Innate Immune Mechanisms of Chronic Airways …...Innate Immune Mechanisms of Chronic Airways Disease A thesis submitted for the degree of Doctor of Philosophy Venkata Sita Rama Raju

Innate Immune Mechanisms of

Chronic Airways Disease

A thesis submitted for the degree of Doctor of Philosophy

Venkata Sita Rama Raju Allam MS (Pharm)

Graduate School of Health

March 2019

ii

CERTIFICATE OF ORIGINAL AUTHORSHIP

I certify that the work in this thesis has not previously been submitted for

a degree nor has it been submitted as part of requirements for a degree

except as part of the collaborative doctoral degree and/or fully

acknowledged within the text.

I also certify that the thesis has been written by me. Any help that I

have received in my research work and the preparation of the thesis itself

has been acknowledged. In addition, I certify that all information sources

and literature used are indicated in the thesis.

This research is supported by the Australian Government Research Training

Program

Signature of Student:

Date: 5th March 2019

Production Note:

Signature removed prior to publication.

iii

ACKNOWLEDGEMENTS

I would like to express my heartfelt thanks to my primary supervisor A/Prof Maria

Sukkar who has been supportive from the starting day of my PhD candidature

and provided me untold opportunities that helped me to become as a critical

thinking student in research. I am also thankful to my co-supervisor A/Prof Sheila

Donnelly for her collaborative work in testing FhHDM-1 in the murine asthma

model and introducing me to the fascinating helminths world.

I would like to thank Dr Shafagh Waters and Dr Ling Zhong for their expertise and

assistance in analyzing the phosphoproteomics data. I would also like to thank

Dr Jane Bourke and Maggie Lam for their collaborative work in performing and

analyzing the ex vivo airway reactivity data using the PCLS technique. I would

also like to thank Dr James Harris, Prof Eric Morand, Stelios Pavlidis, Prof Ian M

Adcock, and Prof Kian Fan Chung for their collaborative work in investigating the

role of MIF in severe asthma. I would also like to thank A/Prof Simon Phipps and

Jennifer Simpson for helping in analyzing the histology data.

I would like to especially thank Joyce To, Mercedes, Peta, Dana, who have

helped me around in the lab on countless occasions. A special thanks to Akane

Tanaka for her support in testing FhHDM-1 in the murine asthma. I would also

like to acknowledge Fiona Ryan and Lalit Overlunde, for their support in Ernst

facility during the mice studies.

It’s my fortune to gratefully acknowledge the support of my friends, Varsha

Komalla and Dr Kamal Dua for their support and generous care throughout the

iv

research tenure. They were always beside me during the happy and hard

moments to push me and motivate me. Thanks also to Sharon and Aini for her

help, motivation, and guidance while working in the lab. Big thanks to all my fellow

colleagues and friends particularly, Kielan, Sarah, Newsha, for their co-operation

and support and company on the weekends.

I would like to express my gratitude to the University of Technology Sydney (UTS)

and Graduate School of Health (GSH) for supporting me throughout my studies

with the UTS International Research Scholarship and GSH postgraduate

research scholarship.

Lastly, I would like to thank my mother and siblings who mean a lot to me for

showing selfless love and supporting me in every occasion. My heartfelt regards

to my uncles Raja Sekhar and Rameswara Prasad for their moral support and

thanks to father in law, mother in law and members of my lovely family who stand

beside me and shared their love and support. I owe thanks to a very special

person, my wife, Vindhya for her continued and unfailing love, support and

understanding during my pursuit of PhD that made the completion of thesis

possible. You were always around at times I thought that it is impossible to

continue, you helped me to keep things in perspective.

v

PUBLICATIONS AND PRESENTATIONS DURING

CANDIDATURE

Published journal manuscripts The parasitic 68-mer peptide FhHDM-1 inhibits mixed granulocytic inflammation

and airway hyperreactivity in experimental asthma

Tanaka A, Allam VSRR, Simpson J, Tiberti N, Shiels J, To J, Lund M, Combes

V, Weldon S, Taggart C, Dalton JP, Phipps S, Sukkar MB, Donnelly S.

The Journal of allergy and clinical immunology (2018)141: 2316-2319.

Proteomic Analysis of Extracellular HMGB1 Identifies Binding Partners and

Exposes Its Potential Role in Airway Epithelial Cell Homeostasis

Wong SL, To J, Santos J, Allam VSRR, Dalton JP, Djordjevic SP, Donnelly S,

Padula MP, Sukkar MB

Journal of Proteome Research (2018)17: 33-45.

Presentations

MIF antagonism restores corticosteroid sensitivity in a murine model of severe

asthma

Allam VSRR, Adcock I, Chung KF, Morand E, Harris J, Sukkar MB

European Respiratory Journal 2018, Vol 52, Issue S62, PA979

DOI: 10.1183/13993003.congress-2018.PA979

A novel peptide from the liver fluke Fasciola hepatica inhibits the mixed

granulocytic airway inflammation in a mouse model of allergic asthma.

Allam VSRR, Tanaka A, Dalton JP, Sukkar MB, Donnelly S.

Respirology 2017, pp. 81-81.

Role Of Pattern Recognition Receptors In The Regulation Of Intrapulmonary

Airway Contraction Following Short-Term Cigarette Smoke Exposure In Mice.

Allam VSRR, Lam M, Sukkar MB, Bourke JE

American Journal of Respiratory and Critical Care Medicine 2017; 195:A6937

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Role of RAGE and TLR4 in the regulation of intrapulmonary airway contraction

following short-term cigarette smoke exposure in mice

Allam VSRR, Lam M, Sukkar MB, Bourke JE

Respirology 2017, TP‐140-140



Horizons Conference 2017



Woolcock Institute of Medical Research Symposium 2018

University of Technology Sydney 3 Minute Thesis (3MT) 2016

University of Technology Sydney 3 Minute Thesis (3MT) 2016

Awards linked to abstracts

Asian Pacific Society of Respirology Travel Award 2017

Asian Pacific Society of Respirology Best Abstract Award 2017

vii

TABLE OF CONTENTS

Certificate of original authorship ..................................................................... ii

Acknowledgements ......................................................................................... iii

Publications and Presentations During Candidature .................................... v

Table of contents ............................................................................................ vii

List of Figures .................................................................................................. xi

List of tables ................................................................................................... xiv

List of Abbreviations ...................................................................................... xv

Abstract ......................................................................................................... xvii

General Introduction ......................................................................................... 1

Overview of asthma .................................................................................. 2

Asthma prevalence and characteristics .................................................. 2

Phenotypes of asthma ............................................................................ 3

Overview of severe asthma ...................................................................... 3

Severe asthma prevalence and characteristics ...................................... 3

Phenotypes of severe asthma ................................................................ 5

Overview of chronic obstructive pulmonary disease (COPD) ................... 6

COPD prevalence and characteristics.................................................... 6

Inflammation in asthma and copd ............................................................. 8

Airway inflammation in asthma ............................................................... 8

Airway inflammation in COPD ................................................................ 9

Overiew of the innate immune system in respiratory diseases ............... 11

TLR4 and RAGE signalling ..................................................................... 14

The role of TLR4 in COPD ................................................................... 16

The role of TLR4 in asthma .................................................................. 20

The role of RAGE in COPD .................................................................. 21

The role of RAGE in asthma ................................................................ 23

Macrophage migration inhibitory factor (mif) .......................................... 24

The role of MIF in asthma .................................................................... 28

Novel therapeutic interventions in the treatment of chronic respiratory

diseases ................................................................................................. 29

viii

Biologics in the treatment of the respiratory diseases .......................... 30

Helminth-derived immunomodulatory molecules .................................... 31

Structural and functional characterization of FhHDM-1 ........................ 35

Hypotheses and aims ............................................................................. 37

References ............................................................................................. 39

RAGE and TLR4 differentially regulate airway hyperresponsiveness – implications in COPD ..................................................................................... 68

Introduction ............................................................................................. 69

Materials and methods ........................................................................... 71

Mouse model of acute smoke exposure ............................................... 71

Assessment of airway reactivity in vivo ................................................ 72

Assessment of airway inflammation ..................................................... 72

Assessment of small airway reactivity using precision cut lung slices .. 73

Statistical analysis ................................................................................ 74

Results ................................................................................................... 74

RAGE, but not TLR4, mediates acute smoke-induced airway

inflammation in mice. ............................................................................ 74

Assesment of small airway reactivity in smoke exposed mice ............. 81

Discussion .............................................................................................. 83

References ............................................................................................. 88

Dual role of RAGE and TLR4 signalling in severe asthma .......................... 94

Introduction ............................................................................................. 95

Materials and methods ........................................................................... 97

Mouse studies ...................................................................................... 97

Lung protein digestion and phosphopeptide enrichment ...................... 98

LC-MS/MS analysis .............................................................................. 99

Data Processing ................................................................................. 100

Bioinformatic analysis ......................................................................... 100

Kinase activity prediction .................................................................... 101

Statistical Analysis.............................................................................. 102

Results ................................................................................................. 102

ix

Combined deletion of RAGE and TLR4 protects against airway

inflammation and airway hyperresponsiveness in severe experimental

asthma ............................................................................................... 102

Impact of RAGE and/or TLR4 gene deletion on signaling pathways

activated in severe experimental asthma ........................................... 111

Analyses of phosphorylation motifs and predicted kinases ................ 118

Impact of RAGE and/or TLR4 gene deletion on protein phosphorylation

in severe experimental asthma .......................................................... 120

Discussion ............................................................................................ 125

References ........................................................................................... 130

Macrophage migration inhibitory factor promotes glucocorticoid resistance in severe asthma ........................................................................ 135

Introduction ........................................................................................... 136

Materials and methods ......................................................................... 137

U-BIOPRED data ............................................................................... 137

Mouse model of severe asthma ......................................................... 138

Measurement of airway hyperreactivity .............................................. 139

Analysis of bronchoalveolar lavage fluid ............................................ 139

Quantification of airway inflammation and mucus production ............. 140

Immunoblotting ................................................................................... 141

Results ................................................................................................. 142

MIF expression is associated with neutrophilic inflammation and

inflammasome activation .................................................................... 142

MIF abundance is associated with reduced expression of the

glucocorticoid-inducible anti-inflammatory protein annexin-A1 ........... 144

MIF inhibition abrogates neutrophilic airway inflammation and increases

glucocorticoid responsiveness in severe experimental asthma .......... 146

MIF inhibition synergizes with glucocorticoid-mediated suppression of

inflammatory gene expression in severe experimental asthma .......... 152

MIF promotion of proteolytic cleavage of ANXA1 ............................... 156

Discussion ............................................................................................ 157

References ........................................................................................... 164

x

The parasitic 68-mer peptide FhHDM-1 inhibits mixed granulocytic inflammation and airway hyperreactivity in experimental asthma ........... 173

Introduction ........................................................................................... 175

Results ................................................................................................. 175

Discussion ............................................................................................ 182

Materials and methods ......................................................................... 183

Synthesis of parasite peptides ........................................................... 183

Preparation and stimulation of bone-marrow derived macrophages

(BMDMs) ............................................................................................ 183

Gene expression profiling and Ingenuity Pathway Analysis® ............. 184

Quantification of cytokines secreted by macrophages ....................... 185

Mouse model of allergic asthma ......................................................... 185

Analysis of Bronchoalveolar lavage fluid ............................................ 186

Quantification of airway inflammation ................................................. 186

Quantification of mucus ...................................................................... 187

Airway hyperresponsiveness (AHR) ................................................... 187

Mouse model of LPS induced neutrophilic inflammation .................... 188

Statistical Analysis.............................................................................. 188

References ........................................................................................... 189

General discussion ....................................................................................... 191

General discussion ............................................................................... 192

Limitations ............................................................................................ 195

References ........................................................................................... 198

Appendices.................................................................................................... 204

APPENDIX I: FhHDM-1 treatment altered genes in macrophages from

microarray analysis .............................................................................. 205

APPENDIX II: FhHDM-1 inhibits cytokine expression in response to LPS

treated BMDMs isolated from C57BL6 mice......................................... 253

APPENDIX III: FhHDM1 inhibits airway neutrophilic inflammation in LPS

treated mice .......................................................................................... 255

LIST OF FIGURES

Chapter 2

Figure 2.1: RAGE, but not TLR4, mediates acute smoke-induced airway

inflammation in mice. ........................................................................................ 76

Figure 2.2: RAGE, but not TLR4, mediates acute smoke-induced increases in

total lung resistance. ......................................................................................... 78


tissue airway dampening. ................................................................................. 79


total elastance. .................................................................................................. 81

Figure 2.5: RAGE and TLR4 do not mediate cigarette-smoke induced changes

in small airway reactivity. .................................................................................. 82

Chapter 3 Figure 3.1: Combined deletion of RAGE and TLR4 protects against granulocytic

airway inflammation in severe experimental asthma. ...................................... 104

Figure 3.2: Combined deletion of RAGE and TLR4 protects against

inflammatory mediator release in severe experimental asthma. ..................... 105

Figure 3.3: Combined deletion of RAGE and TLR4 protects against airway

hyperreactivity in severe experimental asthma. .............................................. 106

Figure 3.4: Quanification of phosphorylated proteins in the lung in severe

experimental asthma. ...................................................................................... 107

Figure 3.5: Volcano plot depicting differential phosphorylation of proteins in

severe experimental asthma. .......................................................................... 108

Figure 3.6. Gene Ontology terms assigned to differentially upregulated

phosphorylated proteins in severe experimental asthma. ............................... 111

Figrure 3.7: Protein-protein interactions for differentially upregulated

phosphorylated proteins in severe experimental asthma. ............................... 114

Figure 3.8: Chemokine signalling KEGG pathway. ......................................... 116

Figure 3.9: Fc gamma R-mediated phagocytosis KEGG pathway. ................. 117

Figure 3.10. Predicted kinase activity in severe experimental asthma. ........... 119

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Figure 3.11. Impact of RAGE and/or TLR4 signaling on protein phosphorylation

in severe experimental asthma. ...................................................................... 121

Figure 3.12: Impact of RAGE and/or TLR4 signaling on protein phosphorylation

in severe experimental asthma. ...................................................................... 122

Figure 3.13: Impact of RAGE signaling on protein phosphorylation in severe


Figure 3.14: Impact of TLR4 signaling on protein phosphorylation in severe


Figure 3.15: Impact of RAGE and TLR4 signaling on protein phosphorylation in

severe experimental asthma. .......................................................................... 125

Chapter 4 Figure 4.1: Expression of innate immune mediators in sputum according to

transcriptomic-associated cluster (TAC) status. .............................................. 143

Figure 4.2 MIF gene expression according to transcriptomic-associated cluster

(TAC) status. ................................................................................................... 144

Figure 4.3: Expression of steroid responsive genes and mediators in sputum

according to transcriptomic-associated cluster (TAC) status. ......................... 145

Figure 4.4. Mouse model of severe experimental asthma. ............................. 147

Figure 4.5: ISO-1 inhibits neutrophilic inflammation and AHR in severe


Figure 4.6 ISO-1 restores glucocorticoid responsiveness in severe experimental

asthma. ........................................................................................................... 151

Figure 4.7: Effects of ISO-1 and/or Dex on tissue inflammation and mucus

secretion. ........................................................................................................ 152

Figure 4.8. Effects of ISO-1 and/or Dex on NLRP3 expression, IL-1β release.

........................................................................................................................ 154

Figure 4.9. Effects of ISO-1 and/or Dex on annexin A1 cleavage. .................. 157

No table of figures entries found.Figure 5.1: FhHDM-1 modulates macrophage

gene expression .............................................................................................. 176

Chapter 5

Figure 5.2: FhHDM-1 protects against allergic airway inflammation ............... 178

xiii

Figure 5.3: FhHDM-1 inhibits allergen-induced airway hyperreactivity. .......... 179

Figure 5.4: FhHDM-1 inhibits allergen-induced tissue inflammation and mucus

production. ...................................................................................................... 180

LIST OF TABLES

Chapter 3

Table 3.1: Differentially phosphorylated proteins in response to PBS and HDM

challenge in WT, RAGE-/- and TLR4-/- mice .................................................... 109

Table 3.2: Interconnected proteins identified in STRING analysis .................. 115

Table 3.3: Enriched KEGG pathway ............................................................... 117

Chapter 4 Table 4.1: Inflammatory mediators in BALF .................................................... 155

Chapter 5 Table 5.1: Chemokine and cytokine expression in BALF ................................ 180

LIST OF ABBREVIATIONS

AGE Advanced glycation end products

AHR Airway hyperresponsiveness

ANOVA Analysis of variance

APCs Antigen-presenting cells

BALF Broncoalveolar lavage fluid

BMDM Bone marrow-derived macrophages

CCL3 Chemokine (C-C motif) ligand 3

CCR1 C-C chemokine receptor type 1

CSE Cigarette smoke extract

DOCK2 Dedicator of cytokinesis 2

ELISA Enzyme linked immunosorbent assay

ERK Extracellular signal-regulated kinase

Ers Total elastance

ES Excretory-secretory

FEV1 Forced expiratory volume in one second

FhHDM-1 Fasciola hepatica helminth defense molecule-1

FVC Forced vital capacity

G Tissue damping

GC Glucocorticoids

GEFs Guanine-nucleotide exchange factors

GILZ GC-induced leucine zipper

GINA Global Initiative for Asthma

GO Gene ontology

GWAS Genome-wide association studies

H Tissue elastance

H & E Hematoxylin and eosin

HBSS Hanks Balanced Salt Solution

HDM House dust mite

IFN-γ Interferon gamma

IL-17 Interleukin 17

IL-1α Interleukin 1 alpha

xvi

IL-1β Interleukin 1 beta




IL-6 Interleukin 6

KEGG Kyoto Encyclopedia of Genes and Genomes

LC-MS/MS Liquid chromatography-tandem mass spectrometry

LPS Lipopolysacchride

MCh Methacholine

MIF Macrophage migration inhibitory factor

MMPs Matrix metalloproteinases

MMPs Matrix metalloproteinases

NF-kB Nuclear factor-kappa B

NLRP3 NACHT, LRR and PYD domains-containing protein 3

PAMPs Pathogen-associated molecular patterns

PAS Periodic Acid Schiff

PBST Phosphate Buffered Saline containing Tween

PCLS Precision cut lung slices

PEEP Positive end-expiratory pressure

RAGE Receptor for advanced glycation endproducts

Rn Newtonian resistance

ROS Reactive oxygen species

Rrs Total Resistance

SARP Severe Asthma Research Program

SEM Standord error mean

SNP Single nucleotide polymorphism

TACs Transcriptomic-associated clusters

TBST Tris-buffered saline containing Tween

TLR4 Toll-like receptor 4

TNF-α Tumor necrosis factor alpha

TRIF TIR-domain-containing adapter-inducing interferon-β

TSLP Thymic stromal lymphopoietin

https://en.wikipedia.org/wiki/Metalloproteinase

xvii

ABSTRACT

The human respiratory tract is exposed to environmental irritants on a daily basis.

The innate immune system is composed of different cellular components

including the resident airway epithelium and macrophages and acts as the first

line of defense to protect the lung against inhaled irritants. Activation of innate

immune pathways is associated with the release of different mediators like

cytokines, chemokines, lipid mediators and complement factors to mediate the

recruitment of different immune cells into the airway lumen. The role of the innate

immune system in chronic airways disease is currently a major area of research

in the field and the focus of this thesis.

RAGE and TLR4 are two major innate immune receptors implicated in the

pathogenesis of asthma and COPD. We used TLR4, RAGE and TLR4/RAGE

deficient mice to study the individual and combined role of these receptors in the

airway response to acute cigarette-smoke exposure. We found that RAGE but

not TLR4 deficiency protected against cigarette-smoke induced neutrophilic

airway inflammation, mediator release and airway hyperreactivity (AHR).

Interestingly, TLR4 deficiency exacerbated AHR. Together these findings,

suggest that RAGE rather than TLR4 should be pursued as a therapeutic target

in COPD.

In contrast to our findings above however, we found that dual inhibition of

TLR4/RAGE signaling, but not individual inhibition of these receptor pathways,

protects against corticosteroid-resistant airway neutrophilia and AHR in an

experimental model of severe asthma. Also, by performing a global

xviii

phosphoproteomics analysis of lung tissue samples, we identified novel signaling

pathways activated down-stream of TLR4/RAGE ligation in severe experimental

asthma.

We also investigated the role of macrophage migration inhibitory factor (MIF) in

severe asthma. We demonstrated increased expression of MIF, S100A8/A9 and

TLR4, and reduced expression of annexin A1 (ANXA1) in subjects with

predominant airway neutrophilic inflammation. We also demonstrated that MIF

inhibition protects against corticosteroid-resistant neutrophilic inflammation and

airway hyperreactivity, and restores corticosteroid sensitivity in an experiental

mouse model of severe asthma. Beneficial effects of MIF inhibition were

associated with inhibition of S100A8 and CCL11 protein in the bronchoalveolar

lavage fluid and reduced proteolytic cleavage of ANXA1. While ISO-1 had no

effect on the secretion of pro-neutrophilic mediators, including IL-1 family

cytokines, it did render these pathways sensitive to inhibition by dexamethasone.

Finally, we identified a role for FhHDM-1, an immunomodulatory peptide derived

from liver fluke Fasciola hepatica as a novel therapeutic treatment for asthma.

Administration of FhHDM-1 protected against eosinophilic and neutrophilic

inflammation, mucus secretion and AHR in a mouse model of house-dust mite

induced asthma.

In summary, the studies in this thesis have uncovered new molecular

mechanisms of innate immune activation associated with the inception and

xix

progression of COPD and severe asthma, and have identified a novel helminth-

based therapy for the treatment of asthma.

1

Chapter 1

GENERAL INTRODUCTION

2

OVERVIEW OF ASTHMA

Asthma prevalence and characteristics

Asthma is a chronic pulmonary non-communicable disease of the conducting

airways resulting in a substantial burden for about 334 million people

worldwide(1). In Australia, the prevalence is estimated at 10%(2), although lower

prevalence is seen in developing countries(3). However, while that prevalence is

becoming substantially stable or decreasing in many developed countries, it is

increasing rapidly in developing countries like China and India due to lifestyle

changes caused by urbanisation(4).

Asthma is a heterogeneous disease characterised by chronic airway

inflammation, airway hyperresponsiveness (AHR) and airway remodelling.

Airway inflammation involves the activation of both the innate and adaptive

immune systems together with the structural epithelial cells to induce the release

of different inflammatory mediators and the influx of inflammatory cells into the

airways(5). Structural airway remodelling is mainly associated with a loss of

epithelial integrity, a thickening of the basement membrane, subepithelial fibrosis,

goblet cell and submucosal gland enlargement, increased smooth muscle mass,

decreased cartilage integrity and increased airway vascularity(6). To diagnose

asthma, a history of repetitive respiratory symptoms is needed, such as

wheezing, coughing, shortness of breath and chest tightness together with limited

expiratory airflow(7). Symptoms can be either induced or triggered by a range of

different factors including environmental stimuli (plant pollens, animal dander and

allergens, such as house dust mites, cockroach extracts), airborne pollutants

3

(smoke and diesel exhaust particles), physical stimuli (cold and exercise) and

medications (aspirin)(8).

Phenotypes of asthma

In early attempts, phenotypes of asthma were classified into two types: allergic

(extrinsic) or non-allergic (intrinsic) asthma, based on the presence of

Immunoglobin E (IgE) antibodies and skin prick testing for inhaled allergens(5).

However, it was later recognized that asthma is not a single disease, but rather a

clinical syndrome where similar characteristic features (phenotypes) can arise as

a consequence of different underlying cellular and molecular mechanisms

(endotypes)(9). Over the years, different clinical subgroups of asthma have been

defined based on the atopic status, symptomatic triggers, patterns of airflow

obstruction and disease severity (10, 11). Based on the induction of triggers,

phenotypes have been classified into allergic, non-allergic, aspirin-exacerbated

respiratory disease, infection-induced and exercise-induced asthma. Based on

inflammatory characteristics, asthma disease has been categorised into

eosinophilic, neutrophilic, mixed granulocytic and paucigranulocytic asthma (12).

OVERVIEW OF SEVERE ASTHMA

Severe asthma prevalence and characteristics

While the majority of patients with asthma have shown effective symptom

improvement using standard therapies recommended by the Global Initiative for

Asthma (GINA)(13), a small fraction (5–10%) of the asthmatics have responded

poorly to this symptomatic treatment that accounts for more than half of asthma-

related healthcare costs(14). In 2014, a consensus definition of severe asthma

4

was published by the European Respiratory Society-American Thoracic Society,

which has drawn a significant distinction between difficult-to-treat asthma and

severe asthma(15). Severe asthma is a subset of difficult-to-control asthma,

which is used to describe patients with asthma that remains uncontrolled despite

treatment with high-dose inhaled glucocorticoids (combined with either a long

acting β2-agonist, a leukotriene modifier or theophylline) for the previous year or

despite treatment with systemic glucocorticoids for at least half of the previous

year(15, 16).

Severe asthma is a complex heterogeneous disease with several underlying

pathologies mainly characterized by persistent airway inflammation with a

dysregulation of Th1/Th2 cytokine production(17, 18), recurrent exacerbations

associated with pathogens, airway remodelling with increased airway smooth

muscle mass and hypertrophy(19), increased epithelial cell proliferation and

thickened epithelium(20). Patients with severe asthma have persistent symptoms

or airflow obstruction that are difficult to control, even with aggressive therapy.

Most of the reasons involved in the management of this poor control asthma

remains unclear, although poor treatment adherence and persistent triggers are

the common causes of severe asthma(21). In addition, comorbidities (such as

allergic rhinitis, chronic rhinosinusitis, gastroesophageal reflux, vocal cord

dysfunction, sleep-related breathing disorders and heart disease) which confound

the disease result in a significant increase in morbidity and frequently contribute

to the treatment of this asthma phenotype(22).

5

Phenotypes of severe asthma

The Severe Asthma Research Program (SARP) analysis of severe asthma,

conducted by the National Heart, Lung, and Blood Institute, has identified three

clinical severe asthma phenotypes in adults that consist of early onset allergic

asthma, adolescent/early adult onset asthma with less reversible/chronic airflow

obstruction and late onset less allergic asthma, which is diagnosed mostly in

obese individuals with high disease impairment but normal lung function (23).

Similarly, two phenotypes have been identified in children using the SARP

analysis. The first cluster is children with an early age onset of asthma who have

atopic features with an increased AHR to methacholine, and also those with

increased airflow limitation who have a high prevalence of comorbidity. The

second cluster is children with an early onset of symptoms accompanied by atopic

features who have partially reversible and more advanced airflow obstruction with

the greatest burden of symptoms, associated medication use and less

comorbidity (23).

Recent studies from Unbiased BIOmarkers in PREDiction of respiratory disease

outcomes (U-BIOPRED) identified three molecular phenotypes termed

transcriptome-associated clusters (TACs). TAC1 was characterized by increased

sputum eosinophils and increased expression of IL33R, CCR3 and TSLPR

genes, TAC2 was characterized by increased sputum neutrophils and increased

expression of interferon, tumour necrosis factor-α and inflammasome-associated

genes. TAC3 was characterized by normal to moderately high sputum eosinophils

and increased expression of genes associated with metabolic and mitochondrial

function (24).

6

OVERVIEW OF CHRONIC OBSTRUCTIVE PULMONARY

DISEASE (COPD)

COPD prevalence and characteristics

COPD is a major cause of morbidity and mortality worldwide and is currently the

fourth leading cause of death worldwide. It is predicted to become the third

leading cause of death by 2030(25). The Global Initiative for Chronic Obstructive

Pulmonary Disease (GOLD) has defined COPD as a disease state characterised

by persistent, and usually progressive, airflow limitation that is not fully reversible.

COPD is clinically diagnosed using lung function spirometry tests that include

forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)

measurements to determine the airflow limitation. The GOLD guidelines stated

that a post-bronchodilator FEV1/FVC ratio of <0.70 and FEV1 of ≤ 70% confirms

the presence of persistent airflow limitation(26). GOLD guidelines further

classified COPD severity into Stage 1 (FEV1 ≥ 80% predicted), Stage 2 (FEV1 =

50-79% predicted), Stage 3 (FEV1 = 30-49% predicted) and Stage 4 (FEV1 <

30% predicted) (GOLD 2018).

COPD has three main components which may coexist or may have one

component in predominance: (1) chronic bronchitis or inflammation in the large

airways; (2) small airways disease featuring inflammation, peribronchiolar fibrosis

and airway obstruction; and (3) emphysema defined as alveolar tissue

destruction, which causes the loss of lung recoil properties(27). Tobacco smoke

is a main risk factor in COPD development, though only 10–20% of smokers are

susceptible to the disease and the reason for this remains unclear(28). Other

7

factors have been shown to be associated with disease prevalence, such as

outdoor, occupational and indoor pollutants (e.g., the burning of biofuels for heat

and cooking) as well as a genetic predisposition(29). While it is suggested that

genetic factors can contribute to the development of COPD, specific genes have

yet to be identified(30, 31). COPD has been associated with a wide range of

symptoms including breathlessness, cough, sputum production, wheezing and

chest tightness with various degrees of severity. These symptoms impose a

substantial burden on the health status, daily activities, physical activity, sleep,

comorbid anxiety and depression of COPD patients, further reducing their quality

of life(32).

AHR itself gained attention as a prognostic factor for an accelerated decline in

lung function and is considered a future risk for COPD in the general

population(33, 34). One study reported that cigarette smoking may lead to

nonspecific AHR because it causes airway inflammation or mucosal permeability

without airway obstruction in humans(35). However, other studies have also

reported that AHR is responsible for the development of chronic airflow

obstruction in asymptomatic smokers(36) and smokers with the early stages of

COPD(37), which is further considered as a risk factor in COPD mortality(38). It

is therefore important to understand the biology of AHR in COPD, as the

mechanisms underlying AHR in COPD are quite different from asthma and were

not responsive to corticosteroid treatment(39).

8

INFLAMMATION IN ASTHMA AND COPD

Airway inflammation in asthma

Airway inflammation has emerged as a major contributor in the pathogenesis of

asthma, which can further mediate the bronchoconstriction and

hyperresponsiveness associated with the disease. Inflammation in asthma is a

complex myriad orchestrated with multi-cellular inflammatory infiltrate associated

with a broad network of self-amplifying mediators, including cytokines,

chemokines, immunoglobulins and growth factors. Although 50% of asthmatics

have the type 2 helper T (Th2) predominant disease with an increase in

eosinophils, asthma is a multifactorial disease and different phenotypes have

been identified with distinct inflammatory statuses(16). For example, Th2

inflammation predominant asthma is characterized by the presence of cytokines

(including the interleukin-4, interleukin-5, and interleukin-13) that were originally

recognized as being produced by Th2 cells(5). These cytokines are also

produced by innate lymphoid cells (which do not express B- or T-cell receptors)

in response to infectious agents and pollutants. As interleukin-4 and interleukin-5

promote the production of IgE and eosinophils, this inflammation is frequently

characterized by increased eosinophils.

Neutrophil dominant asthma afflicts patients diagnosed with increased sputum

neutrophilia without eosinophilia, suggesting the involvement of non-type 2

mediated mechanisms. Neutrophil dominant inflammation is associated with the

secretion of the different cytokines, including IL-17A, IL-17E, IL-17F and IL-22.

The cytokines derived from Th17 cells can also mediate airway smooth muscle

9

proliferation(40) and smooth muscle contraction(41) in humans as well as mice,

suggesting that they play a role in smooth muscle hyperplasia and AHR. CXCL8

has also been proposed as playing an important role in severe neutrophilic

asthma, as levels of CXCL8 correlate with the number of neutrophils in the

sputum of asthmatics(42).

Some asthmatics have mixed granulocytic inflammation with an evidence of both

neutrophilic and eosinophilic inflammation in the sputum. Both IL-6 and IL-17

have played key roles in promoting mixed Th2 and Th17 cell infiltration in

airways(43, 44). In contrast, a specific phenotype termed paucigranulocytic

asthma showed no evidence of increased numbers of eosinophils or neutrophils

in sputum or blood and was not reactive to anti-inflammatory therapies(45).

However, the airflow limitation associated with this phenotype can be driven by

airway structural changes, such as airway smooth muscle tissue hypertrophy(46).

Airway inflammation in COPD

The inflammation associated with COPD involves the activation of both innate

and adaptive immune systems connected with the activation of dendritic cells(47).

COPD associated inflammation with an increase in different inflammatory cells

including neutrophils, macrophages and lymphocytes has been observed in

COPD patients(48). Different structural cells (including the airway and alveolar

epithelial cells, endothelial cells and fibroblasts) also act as primary effector

inflammatory cells in COPD. The associated inflammation in COPD patients looks

similar to the inflammation in smokers without airflow limitation, but is augmented

in COPD patients during the exacerbations or infections. This inflammation also

10

does not resolve, despite smoking cessation suggesting the involvement of

memory adaptive immune response activation in the pathogenesis of COPD(49).

Increased numbers of neutrophils have been found in the broncoalveolar lavage

fluid BALF(50), (51) and in induced sputum samples from COPD patients(52).

Increased sputum neutrophilia is also associated with the presence of greater

airflow obstruction, which promotes an accelerated decline in lung function(53).

Cigarette smoke also impairs neutrophil phagocytic ability by suppressing the

caspase-3, increasing the risk of other respiratory infections in COPD patients.

Macrophages plays a key role in COPD, as smoking activates macrophages,

triggering the potential release of reactive oxygen species (ROS), extracellular

matrix proteins, and lipid mediators (such as leukotrienes, prostaglandins,

cytokines, chemokines and matrix metalloproteinases(MMPs)(54). Macrophages,

along with neutrophils, have also been observed around injured lung parenchyma

in COPD patients(55). Embedded macrophages associated with peribronchial

fibrosis have been observed across the smaller airways of smokers and ex-

smokers as well(56).

Previous studies have shown the involvement of the adaptive immune system in

the pathogenesis of COPD. Different studies have reported an increase in CD8+

T-cell numbers around airways and in lung parenchyma(57), which was

associated with an increase in perforin levels in the sputum(58) and granzyme B

levels in the BALF collected from COPD patients(59). These increases may be

associated with an increase in lung parenchymal damage. Along with the CD8+

11

cells, an increase in activated CD4+ T-cell numbers has been identified in the

small airway walls of smokers with severe COPD(57). However, a reduced

number of T regulatory cells have been seen in COPD patients, which is

associated with the reduced gene expression of forkhead box protein P3 (FOXP3)

in the lungs of COPD patients, a transcription factor crucial for the development

of regulatory T-cells(60) suggesting that anti-inflammatory regulatory

mechanisms are decreased in the pathogenesis of COPD.

While airway inflammation in asthma and COPD has been well characterized,

there remains a substantial need to understand the inflammatory mechanisms

underlying the pathogenesis of these diseases for the purpose of identifying novel

therapeutic interventions. As well, the human acquired/adaptive immune

response to environmental insults has been well characterized, yet the role of

innate immune system activation in the pathogenesis of asthma and COPD

remains unclear. Thus, the focus of this thesis is determining the role of the innate

immune system activation in activating the inflammatory state during the initiation

of asthma and during exposure to environmental stimuli, including allergens and

cigarette smoke.

OVERIEW OF THE INNATE IMMUNE SYSTEM IN RESPIRATORY

DISEASES

An observation made by Strachan regarding the ‘Hygiene hypothesis’ reported

that reduced exposure to different infections during early childhood through

improved living standards and higher levels of personal hygiene might result in

an increased risk of developing an allergic disease later in life(61). This hygienic

12

effect has been shown in a decrease in immunological responses elicited against

infectious agents. In searching for an interface between the hygiene effect and

decreased immune system response, the innate immune system was found to

play a key role in the discrimination between infectious and harmless

environmental components.

The innate immune response is the first line of defence against environmental

insults immediately after exposure. In contrast to adaptive immunity, innate

immune responses are nonspecific and do not require any developmental phase

to mediate function. The innate immune system of vertebrate’s uses three

strategies for immune recognition: the ‘microbial nonself’ that recognizes

conserved products of microbial metabolism unique to microorganisms that are

not produced by the host; the ‘missing self’ that detects the markers of the host

and activates different inhibitory pathways that block the initiation of immune

responses; and the ‘induced or altered self’ that detects the markers of the

abnormal self that are induced upon infection and cellular transformation(62).

The activation of the innate immune system involves multiple molecular

recognition events for the detection of host-pathogen interactions. Different

proteins from the host, which occur as receptors on cells and secreted molecules

that recognize features common to many pathogens, can activate the innate

immune system(63). Receptors of the innate immune system, commonly termed

as pattern recognition receptors (PRRs), are the surface receptors that recognize

and bind to the regular repeating unique molecular patterns of microorganisms,

commonly referred to as pathogen-associated molecular patterns (PAMPs).

13

PRRs, such as the Toll-like receptor (TLR) and Nucleotide-binding and

oligomerization domain like receptor (NLR) families and the receptor for

advanced glycation endproducts (RAGE), engage in response to environmental

stimuli, including foreign microbial proteins and dangerous endogenous stimuli

from host cells. Among PRRs, the importance of TLRs in various respiratory

diseases has been studied (64-68). TLRs have been split into two sub-groups

based on their ligand specificity. TLR1, TLR2, TLR4, TLR5, TLR6 and TLR11 are

primarily expressed on the cell surface to recognize the components of microbial

membranes, while TLR3, TLR7, TLR8 and TLR9 are commonly expressed

intracellularly in vesicles (like lysosomes, endosomes and the endoplasmic

reticulum), which can target microbial nucleic acid(68).

The activation of these receptors regulates different downstream pathways to

induce and release different protein mediators, which activate the inflammatory

response and coordinate cellular and humoral responses aimed at eliminating

invasive microorganisms referred to as cytokines. Different cells (including

epithelial cells, innate lymphoid cells (ILCs), macrophages, dendritic cells (DCs)

and neutrophils) are able to secrete mediators to orchestrate the innate immune

responses(69). These mediators include an array of soluble mediators secreted

by various innate immune cells, such as TNFα, IFNγ, TSLP IL-25, IL-33, IL-1α

and IL-1β. There is vast evidence about the role of cytokines in the pathogenesis

of different chronic respiratory diseases(70, 71). The macrophage migration

inhibitory factor (MIF) is one such cytokine, and was initially defined as a T-

lymphocyte derived cytokine(72) before being shown by other studies as the

14

innate immune cytokine for several diseases including tuberculosis, sepsis and

septic shock(73-76). Roger et al. reported that MIF is an upstream mediator that

regulates the innate immune response through the upregulation of TLR4

expression in LPS-treated macrophages(77). However, the role of MIF as an

innate immune cytokine in the pathogenesis of different chronic respiratory

diseases is poorly studied.

This thesis focuses on investigating the role of TLR4 in the pathophysiology and

pathogenesis of respiratory diseases. As this has not been widely studied, the

following sections describe the importance of TLR4 in chronic lung diseases, such

COPD and asthma. As RAGE is also a pattern recognition receptor that shares

common ligands with TLR4, the role of RAGE must be studied either alone or in

cooperation with TLR4 regarding chronic lung diseases. MIF regulates TLR4

expression, so understanding the role of MIF in regulating the innate immune

system regarding these diseases is also of importance. Therefore, this thesis

focuses on elucidating the role of MIF in the pathogenesis of respiratory diseases,

especially severe asthma.

TLR4 AND RAGE SIGNALLING

TLR4 are type I transmembrane receptors expressed on the surface of different

cells including airway epithelial cells, macrophages and neutrophils. The

activation of TLR4 together with IL-1 receptors forms a complex Toll/interleukin-

1 receptor (TIR), which activates various inflammatory pathways via recruiting

intercellular adapters, including the myeloid differentiation 88 (MyD88) and the

TIR-domain-containing adapter-inducing interferon-β (TRIF)(78). The activation

15

of the MyD88-dependent pathway mediates the induction of inflammatory

cytokines via IRAK family kinases with the downstream activation of nuclear

factor-kappa B (NF-κB), mitogen-activated protein kinases and activator protein

1, whereas the activation of the TRIF-dependent pathway activates the release

of type I interferons (IFNs) using interferon-regulatory factors (IRFs)(64, 79).

Thus, the activation of TLR4 induces inflammatory cell recruitment and cytokine

release to promote the inflammation.

In the presence of the ligand binding, oligomerization of the RAGE at the plasma

membrane is increased to increase downstream signalling(80). The cytoplasmic

domain of RAGE is essential for intracellular signalling and requires a binding

partner, as RAGE lacks the endogenous tyrosine kinase activity. The cytoplasmic

domain of RAGE interacts with diaphanous-1 (Dia-1) to mediate the activation of

small GTPases, including Rac-1 and Cdc42, that promote cell migration(81) and

regulate the expression of the cytokines involved in cell differentiation(82). RAGE

also promotes its intracellular signalling through the phosphorylation of the RAGE

cytoplasmic domain using protein kinase PKCζ. That leads to the recruitment of

different adaptor proteins, including TIRAP and MyD88, which results in the

downstream activation of IRAK4 to trigger signal transducers (including NF-κB,

Akt, p38 and caspase-8) that promote the induction of inflammatory mediators

and growth factors(83). RAGE, via its AGE interaction, is also involved in the

increasing of intracellular ROS to activate downstream signalling pathways,

including small GTPase Ras, and mitogen-activated protein kinases (MAPKs),

such as p38 and JNK(84), to exacerbate inflammation.

16

Given that both TLR4 and RAGE mediate inflammatory responses, it is not

surprising that both have been widely implicated in inflammatory disorders and

chronic lung diseases. However, the roles of TLR4 and RAGE in COPD remain

controversial and unclear. Indeed, there is conflicting evidence in the literature on

the roles of RAGE and TLR4 in CS-induced inflammation and/or the pathogenesis

of COPD.

The role of TLR4 in COPD

Different genomic studies have shown a discrepancy in the association of TLR4

polymorphism in the pathogenesis of COPD. Apostolou et al. have shown that

rs11536889 SNP was associated with early stage COPD, but not with late stage

COPD accompanied by severe lung function decline(85). Another study has

reported that 11 of 17 TLR4 SNPs were associated with FEV1 decline and

increased numbers of sputum inflammatory cells, which suggests TLR4

polymorphism involvement in the severity and progression of COPD(86).

Similarly, Ito and his colleagues have shown the minor C allele of rs11536889

SNP in the TLR4 gene is likely associated with the risk of developing emphysema

in the Japanese cohort(87). This variation in the association of TLR4

polymorphism with COPD severity may be due to different cohorts with various

medical backgrounds used for the studies.

Conflicting evidence has also been reported about TLR4 expression in COPD

patients. Di Stefano et al. have reported an increased protein expression of TLR4

in the bronchial epithelium positively correlated with an increased number of

CD4+ and CD8+ cells and increased airflow obstruction in patients with severe to

17

very severe stable COPD when compared with healthy subjects(88). In contrast,

the MacRedmond group has shown a decreased TLR4 mRNA expression in the

nasal epithelium and trachea brush specimens of smokers and severe COPD

patients(89). Nadigel and his colleagues have shown no change in TLR4 protein

expression in the epithelium and inflammatory cells, but have shown an increase

in the percentage of CD8+ T cells that express the TLR4 protein in endobronchial

biopsy tissue sections from COPD patients when compared to healthy

subjects(90) . Yet another study has reported an increase in TLR4 positive

neutrophils and macrophages in stained mini-broncholaveolar specimens

collected from COPD patients in comparison with smokers and healthy subjects,

showing that TLR4-expressed neutrophils reduces apoptosis(91). In summary,

the studies on the expression of TLR4 in COPD patients are contradictory, but

this could be due to a lack of specificity in considering tissue or cells, or even the

severity of the disease, when determining TLR4 expression.

Not only has this variation of TLR4 expression been observed in human COPD

pathology, conflicting evidence has also been noticed when different cells were

stimulated by cigarette smoke extract. In one such study, Lin and his colleagues

demonstrated an increase in TLR 4 expression in human tracheal smooth muscle

cells stimulated by cigarette smoke extract (CSE) with an associated increase in

NADPH oxidase(92). In contrast, Sarir et al. has shown a down regulated

expression of TLR4 on macrophages associated with increased ROS and IL-8

levels after short term exposure to the cigarette smoke medium(93). Although

both of these studies utilised the different commercial cigarettes with similar

nicotine concentrations for preparing the CSE, they used different concentrations

18

of CSE at different time points to induce inflammation and oxidative stress in the

cells. This demonstrates that the expression of TLR4 depends not only on the

cellular phenotype, but also on the type of insult exposure the cells receive.

The discrepancies observed in the genomic, human and in vitro smoke exposure

studies may be due to differences in the experimental tissues used to see the

expression (e.g., macrophages and smooth muscle cells), differences in the

cohorts of patients with varying medical backgrounds and potential tissue

specificity issues with TLR4 expression. To unravel the mechanisms of how TLR4

is involved in the pathogenesis of COPD, different mouse models have been

used. Previous studies have reported that eight weeks of cigarette smoke

exposure led to an increase in TLR4 mRNA expression in the lungs of the smoke

exposed mice(94). In contrast, Haw et al. did not find any significant increase in

TLR4 mRNA expression in the lungs of mice under similar circumstances, but

they reported an increased expression of TLR4 mRNA in the blunted dissected

small airways of the smoke exposed mice(95). Despite similar exposure times,

the discrepancies in the observed TLR4 expression in the lungs may have been

due to the exposure methods and type of mouse strain used in the experimental

models.

Different studies have also been performed using TLR4-deficient mice to

determine the role of TLR4 in altering inflammation status when the mice were

exposed to cigarette smoke. A significant protection against smoke-induced

inflammation, with decreased neutrophil influx and reduced levels of inflammatory

mediators, was reported in the TLR4-deficient mice(96, 97). In contrast, exposing

19

the TLR4-deficient mice to chronic smoke exposure did not show any significant

protection against the inflammatory status, suggesting that TLR4 is required to

mediate inflammation at the initiation of COPD, but it is not necessary in mediating

the progression of the disease.

Previous studies have also demonstrated the role of TLR4-deficient mice

regarding the emphysematous changes in the lungs of mice with and without

smoke exposure. TLR4 has functioned in maintaining mouse lung homeostasis

by inhibiting the upregulation of the NADPH oxidase enzyme and preventing

oxidant stress, and TLR4 deficiency in mice has also been shown to cause age-

related spontaneous pulmonary emphysema associated with an increased

oxidant stress and cell death in aged mice(98). However, in the presence of

chronic smoke exposure, An et al. have demonstrated that the combined effect

of TLR4 deficient mice with smoke exposure exhibited a marked increase in

airspace enlargement relative to wild-type mice(99) These results are contrary to

the recent study published by Haw et al., who have demonstrated a significant

inhibition on smoke-induced emphysema, alveolar enlargement, apoptosis and

impaired lung function in TLR4-deficient mice(95). That being said, the mouse

background strain used by Haw et al. for the generation of TLR4-deficient

knockout mice is different from the previously reported studies.

Although TLR4 has a significant role in mediating acute smoke-induced

inflammatory response and emphysematous changes during the progression of

COPD, no one has studied its role in smoke-induced AHR, one of the risk factors

20

of human COPD. Thus, investigating the role of TLR4 in mediating smoke-

induced AHR is important and requires further investigation.

The role of TLR4 in asthma

Several genomic studies have emphasised the importance of TLR4 in asthma

pathogenesis. TLR4 SNPs were found to be strongly associated with the

prevalence and risk of asthma development in children (100). Moreover, the TLR4

polymorphism Asp299Gly was associated with a four-fold higher prevalence of

asthma in Swedish school-aged children (101). Although TLR4 has been

implicated in genetic studies using candidate driven approaches, the genomic

wide significance has not been studied in asthma.

These findings were supported by human and mouse studies that investigated

the expression of TLR4 in different compartments of the lung tissue in asthma

patients. Hammad et al. have shown the absence of TLR4 on airway structural

(epithelial) cells (but not haematopoietic cells), significantly reduced HDM-

induced airway inflammation and reduced production of pro-inflammatory

cytokines in BALF (102). It has also been shown that intrapulmonary

administration of a TLR4 antagonist reduced inflammatory cell numbers and pro-

inflammatory cytokine production in BALF, with peri-bronchovascular

inflammation and reduced AHR in sensitised mice. Moreover, Dabbagh and his

team have shown that TLR4 is required on dendritic cells for inducing optimal Th2

responses, showing that mice with TLR4 deletion expressed lower levels of

CD86, a costimulatory molecule important for Th2 responses (103). These

findings were also supported by another study in which HDM-induced AHR was

21

suppressed in sensitised mice deficient in TLR4, and was also associated with

reductions in the numbers of inflammatory cells infiltrating the airways (104). In

addition, Phipps and his colleagues have shown that HDM induce Th2 and Th17

responses to promote allergic inflammation and AHR in the mice via a TLR4/IL-1

dependent manner (105). Moreover, TLR4 was also shown to promote the

contraction of primary human airway smooth muscle cells isolated from

asthmatics, and this effect was inhibited when cells were treated with a TLR4

antagonist(106). In conflict to these studies, Hollingsworth et al. have reported

that being deficient in TLR4 exaggerated allergic airway inflammation and AHR

in an experimental model of ovalbumin-induced asthma, further showing that a

lack of TLR4 leads to increased pulmonary dendritic cells (107).

Although many of these models have shown the importance of TLR4 in mediating

inflammation and AHR in different models of asthma, no one has ever studied the

role of TLR4 involving in the pathogenesis of severe asthma, which requires

further investigation.

The role of RAGE in COPD

RAGE is abundantly expressed in the lungs, maintaining lung homeostasis.

Alterations of RAGE expression in the lungs may cause a disturbance in lung

homeostasis, involving pathophysiological changes in the lungs, as shown in

previous studies where a loss of RAGE expression in the lungs led to idiopathic

pulmonary fibrosis (IPF)(108). Previous evidence suggests a role for RAGE and

its ligands in chronic airway inflammatory disorders. Genome-wide association

studies (GWAS) have identified a single nucleotide polymorphism in the RAGE

22

gene AGER (rs2070600) that is associated with better lung function, as indicated

by the higher FEV1/FVC ratio in the general population compared to patients with

COPD(109, 110).

Different ligands, like HMGB1(111) and S100 proteins(112), associated with the

increased expression of RAGE were observed in the BALF and blood of COPD

patients, respectively. Moreover, an increased expression of RAGE, AGEs and

HMGB1 in the submucosa, epithelium and smooth muscle of the bronchial wall

as well as in alveolar macrophages were observed in smokers with COPD(113).

Furthermore, smoking alone increases RAGE and its ligand expression in airway

mucosal cells of healthy smokers(111) and in the lungs of smoke exposed

mice(114). Different experimental models using RAGE-deficient mice showed a

significant protection against elastase-induced emphysema(115) and COPD-like

changes induced by chronic smoke exposure in mouse models, supporting a role

for this receptor in COPD pathogenesis(116-119).

While different studies have proven the importance of RAGE and its ligands in

COPD pathogenesis and other smoke-related conditions, the soluble form of

RAGE (sRAGE) behaves in a different fashion, showing protection against COPD

pathogenesis. Decreased levels of sRAGE were observed in the blood circulation

of COPD subjects when compared with healthy subjects, which is associated with

declining lung function(120, 121). Although, human and mouse studies have

shown importance of RAGE in mediating inflammation and lung function, the

importance of RAGE’s involvement in mediating AHR in COPD etiology still

remains unclear and requires further investigation.

23

The role of RAGE in asthma

A small number of studies have investigated the role of RAGE in asthma.

Although considerable evidence has shown an increased expression of RAGE

ligands in the airways of asthma patients(122-124), whether there is increased

RAGE expression or activity in asthmatic airways is not yet known. Zhou et al.

have shown increased levels of both HMGB1 and RAGE positively correlated with

an increased percentage of neutrophils in the induced sputum collected from

asthmatics when compared to healthy subjects(125). However, both systemic

and BALF levels of sRAGE were significantly lower in neutrophilic asthma/COPD

samples compared with non-neutrophilic disease(121).

While human studies have shown the importance of RAGE in asthma, different

researchers have used RAGE-deficient mice and RAGE antagonists to show the

protection provided against the pathogenesis of asthma. Milutinovic et al. were

the first to demonstrate that a deficiency of RAGE or an administration of sRAGE

in mice showed protective effects against HDM-induced inflammation and

AHR(126). Similar studies have reported that a deficiency in RAGE caused an

impairment in the activation of the adaptive immune response by impairing T cell

activation and reducing the infiltration of inflammatory cells into the airway lumen

in ovalbumin-induced asthma(127). Oczypok et al. have shown that absence of

RAGE prevents the influx of house dust mite and Alternaria Alternata extract

infiltration of innate lymphoid cells 2 (ILC2) into the airway lumen, preventing the

release of IL-33 to induce asthmatic symptoms in the mice (128). Other

investigators have reported that a lack of RAGE on the structural cells developed

24

spontaneous AHR in naïve mice, demonstrating that RAGE on the structural cells,

but not the hematopoietic cells, was necessary to induce allergic airway disease

(128, 129). In contrast, our lab has shown that the adaptive transfer of HDM-

pulsed RAGE positive dendritic cells to RAGE-deficient mice induced allergic

responses after an HDM challenge in the mice(130), suggesting that the presence

of RAGE, both on the structural and hematopoietic cells, is important to the

induction of the airway inflammatory disease in response to allergens. Though

different studies have demonstrated the role of RAGE in mediating inflammation

and AHR in different models of asthma, no one has yet reported on the important

role of RAGE in the pathogenesis of severe asthma, which requires further

investigation.

MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF)

MIF is an immunoregulatory protein that acts as a critical component of various

inflammatory diseases. Although T lymphocytes were initially thought to be the

main source of the MIF that prevents the migration of macrophages out of

capillary tubes(72), much research has been done since then that has found MIF

in other cells, such as macrophages, neutrophils, eosinophils, mast cells,

basophils, blood dendritic cells and B cells(131, 132). Growing evidence has

suggested that MIF functions not only as a proinflammatory cytokine, but also as

a hormone that possesses enzymatic activity involved in inflammation-associated

pathophysiology.

MIF exerts its biological actions via both receptor and non-receptor

interactions(133). MIF activates different signal transduction pathways via the

25

CD74, a cell surface type II transmembrane protein receptor, where MIF binds to

the extracellular domain of the CD74/CD44 complex to initiate the signal

transduction pathways, including the activation of extracellular signal-regulated

kinase-1/2 MAP kinase cascade (ERK1/2), cell proliferation and prostaglandin E2

production(134). MIF also functions as a chemokine to promote leukocyte

recruitment via interactions with CXCR2 and CXCR4 receptors(135). Beyond its

receptor interactions, MIF performs cell-cycle regulation by antagonizing the

Jab1-dependent cell-cycle regulation via different mechanisms, inhibiting the

activation of AP-1 transcription and increasing p27Kip1 expression(136).

Unlike other cytokines, MIF is capable of two distinct enzymatic activities, one of

which is a tautomerase that requires N-terminal Proline (P2) to catalyse the

tautomerisation of the non-physiological substrates D-dopachrome and L-

dopachrome methyl ester into their corresponding indole derivatives(137).

Lubetsky et al. have reported that this tautomerase active site of MIF is

responsible for the biological activity of MIF, using a mutant form which blocks

the binding site to inhibit catalytic activity (138). As most of the identified MIFs

have P2, these are commonly predicted to have the tautomerase activity that

allows for the development of high-affinity small-molecule MIF inhibitors that can

target this enzymatic site to modulate MIF activities. An oxidoreductase activity

of MIF has also been identified which requires the CXXC motif at the C-terminus

C-A-L-C, comprising amino acids 57 through 60 of the MIF protein, and it has

been reported that this activity is necessary for MIF-mediated immune

processes(139).

26

Several studies have supported the claim that MIF is either directly or indirectly

involved in activating the innate and adaptive immune system. Roger et al. have

reported that MIF-deficient macrophages reduced the activity of PU.1, a

transcription factor required for optimal expression of the Tlr4 gene, and regulates

the expression of TLR4 protein(77). MIF is not only involved in the modulation of

the TLR4 receptor, but is also involved in the production of many pro-

inflammatory mediators including different cytokines, such as IL-1β, IFN-γ,

tumour-necrosis factor (TNF), IL-2, IL-6, IL-8, macrophage inflammatory protein

2(140-144), nitric oxide (NO)(145, 146), cyclooxygenase 2 (COX2) and other

elements of the arachidonic acid pathway(147, 148). Recent studies have also

shown that MIF regulates the release of IL-1α, IL-1β and IL-18 via the activation

of the NLRP3 inflammasome in LPS-treated bone marrow-derived macrophages

(BMDM)(149). Thus, MIF has a crucial role in the inflammatory response after

exposure to pathogenic molecules, other pro-inflammatory cytokines and

antigen-specific stimulation.

In addition to activating the immune system, MIF is also involved in counter-

regulating the anti-inflammatory effects of glucocorticoids (GC) that results in GC

resistance, a major concern in several chronic inflammatory diseases including

rheumatoid arthritis, COPD and severe asthma(141). Different genomic studies

in humans have revealed the role of MIF polymorphisms and its association with

GC resistance in rheumatoid arthritis(150) and nephrotic syndrome(151). It was

also reported that an increased expression of MIF in the mononuclear cells

isolated from colons of patients with GC-resistant ulcerative colitis, and further

treating the cells with anti-MIF antibodies, restored GC-mediated anti-

27

inflammatory effects(152). Previous studies in mouse models have shown the

role of MIF-mediated GC antagonist effects, where exogenous MIF overrides GC-

inhibited lethality in a mouse model of endotoxemia(141) and a dexamethasone-

mediated suppression of inflammation in a mouse model of rheumatoid

arthritis(153). Thus, MIF and GCs act reciprocally in controlling the regulation of

inflammation in different inflammatory diseases.

Although the mechanisms behind this reciprocal relationship have not been fully

elucidated, it has been shown that MIF inhibits GC-induced MKP-1 expression in

LPS or with LPS plus phorbol 12-myristate 13-acetate stimulated RAW 264.7

macrophages(154). A recent study by Fan et al. has reported that MIF negatively

regulates GC-induced leucine zipper (GILZ), which inhibits the expression of

MKP-1, consequent MAPK phosphorylation and cytokine release in a mouse

model of arthritis(155). The second mechanism that MIF antagonizes in GC-

induced anti-inflammatory effects is that MIF downregulates the induction of IκB

in LPS-stimulated human peripheral blood mononuclear cells(156). The third

mechanism that MIF overrides in the anti-inflammatory effects of GC is the

activation of cPLA2, which is strongly inhibited by GCs through the induction of

annexin-1(157).

A little is known about the MIF and its associations with asthma or COPD, despite

the advances in MIF biology and the development of newer antagonists.

Therefore, the following sections focus on the evidence of MIF in chronic lung

diseases, such as asthma.

28

The role of MIF in asthma

Rossi et al. provided the first evidence of increased MIF levels in BALF obtained

from asthmatic subjects, as compared to non-atopic volunteers, and

demonstrated that eosinophils are an important source of MIF(158). Later studies

have reported increased MIF in serum and induced sputum levels, which were

then correlated with increased levels of eosinophil cationic protein in induced

sputum from asthmatics when compared to healthy subjects(159). Mizue and his

colleagues demonstrated the association of the MIF allele with mild asthma,

suggesting an additional role for MIF as a critical mediator in the pathogenesis of

asthma(160).

Using different experimental models of asthma allowed several studies to

investigate the role of MIF in pathogenesis of asthma. Mizue et al. used MIF

knockout mice to demonstrate the importance of MIF in mediating CD4+ T cell

activation and Th2 priming for inducing allergic responses in an ovalbumin-

induced mouse model of asthma(160). Continuing in this vein, Wang et al. used

MIF knockout mice to demonstrate that mast cell-derived MIF was essential for

CD4+T cell activation to induce the allergic airway responses in an ovalbumin-

induced mouse model of asthma(161). In contrast, another study demonstrated

that although MIF knockout mice have shown its protective effects against allergic

airway inflammatory and AHR response, MIF was not essential for ovalbumin-

induced Th2 differentiation(162). Other studies using MIF antibodies and MIF

small molecule inhibitors have shown that MIF is a critical mediator in the

pathogenesis of asthma, mainly by inhibiting eosinophil infiltration and its

associated cytokines(163-166).

29

Although different studies have demonstrated the role of MIF in mitigating GC-

induced anti-inflammatory effects, no one has studied this effect in the context of

severe asthma where GC resistance is a hallmark in its treatment. Thus,

measuring MIF and investigating the therapeutic effect of the small molecular

inhibitors of MIF in an experimental model of severe asthma may provide a

rationale for novel therapeutic strategies in the treatment of severe asthma.

NOVEL THERAPEUTIC INTERVENTIONS IN THE TREATMENT

OF CHRONIC RESPIRATORY DISEASES

Currently, the treatment for asthma includes a regimen of inhaled corticosteroids

with or without long-acting β-agonists, which can improve both symptoms and the

frequency of exacerbations(167). The addition of leukotriene modifiers and long-

acting anticholinergics can be beneficial for patients whose asthma remains

poorly controlled. A failure to respond to these medications has been observed in

some asthma patients due to poor adherence or underlying disease

heterogeneity. Corticosteroids also have considerable side effects including

adrenal insufficiency, weight gain, hypertension, cataracts, glaucoma, systemic

toxicity and osteoporosis(168). Similarly, treatments for COPD are aimed to treat

the symptomatic disease and decrease exacerbations to improve quality of life.

Multiple therapies, including short- and long-acting bronchodilators,

anticholinergics, methylxanthines and corticosteroids, are used as single agents

or, more commonly, in combination to treat the symptoms of COPD patients(169,

170). A number of problems have arrived during new drug treatment discoveries

for chronic respiratory diseases because of heterogeneity in the pattern of airway

30

inflammation, the presence of other comorbidities and the heterogeneity of

exacerbations(171). Therefore, it is necessary to identify new therapeutic

interventions to meet the unsatisfied needs for chronic respiratory disease

treatment.

Biologics in the treatment of the respiratory diseases

A better understanding of inflammation in the pathogenesis of diseases is

essential, as targeting airway inflammation provides a rationale for exploring

novel biologics that selectively block inflammatory pathways(70). Targeting

eosinophils is widely recognized, as eosinophilic airway inflammation is seen

regularly in patients with asthma, and studies have shown that up to 40% of

COPD patients have elevated induced sputum eosinophil levels(172). Different

monoclonal antibodies targeting IL-5, including mepolizumab and reslizumab,

have been used to treat severe eosinophilic asthma and eosinophilia in

COPD(173, 174). An anti-IL5R antibody, benralizumab, also acts on the α-

subunit of the IL5 receptor expressed on eosinophils and basophils targeted in

both severe asthma and COPD(175) and dupilumab, a monoclonal antibody

directed against the a-subunit of the IL4 receptor, inhibits both IL4 and IL13

signalling(176). Moving beyond targeting the Th2 environmental, novel

biologicals have been discovered, such as tezepelumab, an IgG2 monoclonal

antibody that binds to TSLP, (an innate cytokine secreted from the epithelial

cells). Tezepelumab prevents interaction with the TSLP receptor complex, which

has shown effectiveness in early and late asthmatic responses(177).

Neutrophilic inflammation is also viewed as a potentially treatable trait, along with

eosinophilic inflammation, in severe asthma and COPD patients(178, 179).

31

Several cytokines and neutrophil chemokines associated with neutrophilic airway

inflammation have become potential targets for the biological treatment of

respiratory diseases. Infliximab, a monoclonal antibody for TNF-α, has

demonstrated a therapeutic benefit against refractory asthma, but had no

observable effect on health status, lung function or severe exacerbation

frequency in COPD patients(180, 181). Similarly, canakinumab, which neutralises

IL-1β and ABX-IL8 that blocks the IL-8 (a key cytokine involved in neutrophil

recruitment), was shown to have no to modest benefit against the symptoms of

COPD(171). Thus, the efficacy of these biologics has been disappointing and

inhibiting targeted cytokines by using biologics has led to adverse events,

diminishing enthusiasm for their use in the treatment of chronic respiratory

diseases(182).

Currently available biologics targeting single inflammatory mediators are failing

to treat chronic inflammatory respiratory diseases effectively, as the diseases

possess a myriad of inflammatory networks. The biologics used in the treatment

of the respiratory diseases possess different adverse effects, are not physically

stable and are expensive. Therefore, the development of new easily targetable

molecules possessing minimum adverse effects at an effective cost is necessary

to inhibit the inflammatory-derived pathways in the pathogenesis of the

respiratory diseases.

HELMINTH-DERIVED IMMUNOMODULATORY MOLECULES

It has been suggested that helminth and its derived molecules possess potent

immunomodulatory capacities that can be used to treat experimental

32

inflammatory diseases. Helminths can secrete or excrete various molecules into

a mammalian host environment during their interaction, which are termed as

excretory-secretory (ES) products. ES products are composed of proteins,

carbohydrates and lipids(183), which are involved in several processes including

tissue invasion, altering the metabolism to the host environment, creating an

environment in the host and skewing the host’s immune responses towards

tolerance(184). These ES products act as first-line molecules, interacting with

host cell surface receptors and affecting the host immune system. Animal studies

have shown the potent immunomodulatory effects of various ES products on the

pathogensis of many inflammatory and autoimmune diseases by reducing the

intestinal inflammation in colitis models, attenuating Th1-mediated autoimmune

diabetes in NOD mice, reducing the development of clinical EAE symptoms in a

mouse model of MS and blocking the induction of collagen-induced arthritis(185).

Among ES products, cystatins are the best studied immunomodulatory proteins

commonly found in the secretome from a variety of helminths(186) that can inhibit

cysteine proteases, such as cathepsins and aspartyl endopeptidases, which can

interfere with the function of antigen-presenting cells (APCs) and inhibit T cell

activation(187). The helminth-derived cystatins also inhibit T cell proliferation by

stimulating the release of IL-10(188). ES products from these helminths can also

influence Th2 and T regulatory cell differentiation to promote the anti-

inflammatory status of autoimmune diseases, suggesting the therapeutic

potential of these products to treat the autoimmune diseases(189). In the context

of respiratory diseases, the therapeutic potential of ES products have been

demonstrated in different mouse models of asthma, which showed protection

33

against ovalbumin-induced eosinophilic inflammation and airway hyperreactivity,

reduced peri-bronchial inflammation, increased T regulatory cell proliferation and

induction of the anti-inflammatory IL-10 secretion(183). Along with cystatins,

glutathione S-transferases (GSTs) are also seen in the secretome of different

helminths which attenuate the immune mediated oxidative stress(190). Different

recombinant products of the GSTs have gained attention of using these products

as the the immunotherapy vaccines and as therapeutic anti-helminthic drugs in

the treatment of colitis and Crohns disease (191, 192)

Previous studies have shown the therapeutic potential of crude ES products from

numerous helminth parasites by suppressing inducible lung inflammation in

mouse models(193-195). A large portion of ES products derived from helminths

contain complex and unique glycans that possess highly antigenic moieties,

which can induce anti-glycan antibody responses. The usage of purified helminth-

derived products would be beneficial in preventing immune system activation

against non-selective unique glycans. However, only a small number of purified

ES immunomodulatory molecules have been characterized, and fewer proteins

have been demonstrated to protect against airway inflammation in asthma. A

previous study has reported on the therapeutic efficacy of ES-62, a glycoprotein

from filarial nematode Acanthocheilonema viteae, against ovalbumin-induced

airway inflammation by altering the Th cell polarization associated with an

increase in Tbet population(196). Similarly, AvCystatin, a purified cystatin

protease inhibitor of Angiostrongylus cantonensis(197), and anti-inflammatory

protein-2 (AIP-2)(198), a recombinant protein isolated from Ancylostoma

caninum, also ameliorated lung eosinophilic inflammation in rodent models of

34

asthma by inducing interleukin-10 (IL-10)-producing macrophages and regulating

the T regulatory cell proliferation, respectively, reducing Th2 inflammation. In

another study, H polygyrus alarmin release inhibitor (HpARI), a purified ES

protein derived from Heligmosomoides polygyrus, showed a protective effect

against Alternaria alternata-induced asthma by diminishing the activity of IL-33

and preventing the infiltration of eosinophils and ILC2 into the lungs(199).

Similarly, the purified protein PAS-1, derived from the Ascaris suum, was shown

via modulation of IL-10 and IFNγ to significantly attenuate eosinophilic infiltration

by downregulating the Th2 cytokines and IgE production(200). Thus, various ES

products have demonstrated therapeutic benefit against eosinophilic airway

inflammation in different models of asthma.

However, the role of ES-derived products in attenuating neutrophilic inflammation

is not clear and requires further investigation. The neutrophil inhibitory factor

(NIF), a purified protein derived from Ancylostoma caninum, was initially reported

as showing a dominant response against neutrophil infiltration in an acid-induced

lung injury model, but it did not target the neutrophil infiltration, instead blocking

eosinophil recruitment and related Th2 cytokines in an ovalbumin-induced mouse

model of asthma(201). Thus, identifying new ES products that target both

eosinophils and neutrophils is necessary to treat asthma effectively. Furthermore,

the earlier demonstrated experiments in the literature have used ovalbumin, an

inert allergen, which does not induce asthma in humans. While no studies has

demonstrated the therapeutic efficacy of the worms and derived molecules in

mouse models of asthma using clinically relevant allergens, like house dust mite

allergen, to induce the disease which requires further investigation.

35

Helminths also secrete other bioactive molecules that have cathelicidin structure

moiety and possess potent antimicrobial activity(202). These small antimicrobial

peptides possess immunomodulatory capacities, termed as helminth defence

molecules (HMDs). This new family of bioactive peptides are mainly secreted by

trematodes, which possess biochemical and functional similarities to the host

defence peptides that modulate the host immune defence(203, 204). However,

no one showed the therapeutic activity of these peptides against airway

inflammation. Our team has characterized a specific helminth-derived

immunomodulatory peptide, termed as FhHDM-1, which possesses cathelicidin

like structure without anti-microbial activity, but has shown immunomodulatory

effect against different inflammatory diseases(205). The next part of this chapter

focuses on the structural and function characterization of this FhHDM-1 peptide.

Structural and functional characterization of FhHDM-1

FhHDM-1 is a helminth defence molecule secreted from a liver fluke trematode,

Fasciola hepatica. This helminth parasite infects a wide range of hosts, including

humans, cattle, sheep, buffalo, goats, rats, mice and rabbits(206). FhHDM-1 is a

8kDa immunomodulatory peptide that has a cathelicidin-like structure and

possess α-helical moiety(207). In the presence of parasite Cathepsin-L, FhHDM-

1 was cleaved to release a C-terminal fragment of 34-residue peptide (FhHDM-1

p2) that contained a 21-residue amphipathic helix, a stable structure resistant to

pH and other helix-degrading agents, and structurally resembled the bioactive LL-

37 human peptide, a widely studied cathelicidin that is commonly expressed by

inflammatory cells in response to microbes and proinflammatory mediators (204).

36

FhHDM-1 showed its activity by entering into the macrophages through

endocytosis via interacting with the phospholipids of the plasma membrane and

binding to the lipid rafts of the membrane(204). Once internalization occurred,

FhHDM-1 was then cleaved by the lysosomal to release a C-terminal peptide that

had a conserved amphipathic helix. This amphipathic helix prevents the

acidification of the endolysosomal compartments by inhibiting the vacuolar

ATPase (vATPase) and preventing the macrophage from functioning in response

to insults (204).In addition, FhHDM-1 also binds directly with LPS and prevents

its interaction with TLR4 receptors on the macrophages to show its anti-

inflammatory activity against the LPS-induced release of TNF-α and IL-1β(207).

In the recent studies, it was demonstrated that FhHDM-1 prevents the lysosomal

acidification and impairs the activation of the cysteine protease Cathepsin B,

which activates the NLRP3 inflammasome. Inhibiting the NLRP3 inflammasome

attenuates IL-1β production and inhibits the Th1-mediated proinflammatory

activation(208). Thus FhHDM-1 targets the NLRP3 inflammasome activation

which plays a key role in mediating the asthma pathogenesis(209) further give us

a hope that FhHDM-1 can inhibit the airway inflammation which needs further

investigation.

37

HYPOTHESES AND AIMS

RAGE and TLR4 are major pattern-recognition receptors implicated in the

pathogenesis of asthma and COPD. Although they share some common ligands

and signalling pathways, no studies to date have examined whether they act in a

co-operative manner in the airway immune response to environmental triggers of

asthma and COPD. Also, their role in specific disease traits in COPD (eg AHR)

and corticosteroid-resistant severe asthma have not previously been

investigated. Thus, we hypothesised that that RAGE signalling, either alone or

in co-operation with TLR4, contributes to airway inflammation and AHR in COPD

and corticosteroid-resistant features of severe asthma.

MIF is an innate cytokine that counter-regulates the anti-inflammatory activity of

corticosteroids. Although MIF is implicated in asthma pathogenesis, no studies to

date have examined whether MIF is an important mediator of corticosteroid-

resistant severe asthma. We hypothesized that MIF is a mediator of

corticosteroid-resistant airway neutrophilia and AHR in severe experimental

asthma.

FhHDM-1 is an immunoregulatory peptide derived from the Fasciola hepatica

with demonstrated therapeutic potential in murine models of type I diabetes and

multiple sclerosis. However, its anti-inflammatory activity in asthma has not been

investigated. We hypothesised that FhHDM-1 protects against granulocytic

airway inflammation and AHR in an experimental model of allergic asthma.

38

Thus, the aims of this thesis are to:

1. Investigate whether TLR4 and/or RAGE signalling mediates the airway

inflammatory response and AHR in an acute model of cigarette-smoke

exposure (Chapter 2)

2. Investigate whether TLR4 and/or RAGE signalling mediates

corticosteroid-resistant features of disease in a mouse model of severe

experimental asthma (Chapter 3)

3. Determine whether MIF contributes to the development of corticosteroid-

resistant neutrophilic inflammation and AHR in severe experimental

asthma (Chapter 4)

4. Investigate the anti-inflammatory role of FhHDM-1 in an acute mouse

model of house dust mite induced asthma (Chapter 5)

39

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68

Chapter 2

RAGE AND TLR4 DIFFERENTIALLY REGULATE

AIRWAY HYPERRESPONSIVENESS – IMPLICATIONS

IN COPD

69

INTRODUCTION

Chronic obstructive pulmonary disease (COPD) is characterised by progressive

loss of lung function and deterioration in health status. While cigarette smoking

is one of the major risk factors for the development of COPD, several host factors

including genetic background, low lung function and airway hyperresponsiveness

(AHR) also contribute to COPD risk (1). Currently, there is significant interest in

the role of the receptor for advanced glycation end products (RAGE) in COPD as

it is a genetic determinant of low lung function and COPD susceptibility and is

also involved in the cellular and molecular response to cigarette smoke exposure

(1, 2).

Increased RAGE protein expression is observed in bronchial biopsy tissue from

smokers with COPD, compared to smokers without COPD and never smokers

(3). Moreover, studies using experimental mouse models of COPD have

demonstrated a role for RAGE in the development of neutrophilic airway

inflammation and emphysema, both of which are key phenotypic features of the

disease (4-8). AHR, defined by an exaggerated response of the airways to

specific and non-specific stimuli is an independent phenotypic trait in COPD

associated with the neutrophilic response (9). However, despite considerable

investigation of the ligand-RAGE axis in COPD, and its known function in

neutrophil trafficking (10-12), its role in the development of AHR in COPD has not

been investigated.

RAGE is a pattern-recognition receptor that interacts with a broad repetoire of

endogenous ligands such as HMGB1 and the heterodimeric complex

70

S100A8/A9, which are also reported to be elevated in COPD (3, 13, 14).

Importantly, while HMGB1 and S100A8/A9 are important RAGE ligands they also

signal via toll-like receptor 4 (TLR4), a major pattern-recognition receptor

implicated in COPD (15). Increased levels of TLR4 protein are observed in the

bronchial mucosa of patients with stable COPD, compared to nonsmoking control

subjects (16), while studies in mice have demonstrated a role for TLR4 in the

acute neutrophilic response to cigarette smoke exposure (17-21). Notably,

previous studies have shown that HMGB1 facilitates the pro-inflammatory activity

of the TLR4 ligand LPS in a RAGE-dependent manner, indicating functional co-

operation between RAGE and TLR4 signaling (22). Indeed, this notion is further

supported by evidence that RAGE utilizes the TLR4 adaptor proteins TIRAP and

MyD88 to mediate its biological effects (23).

We hypothesise that RAGE signalling, either alone or in co-operation with TLR4,

contributes to AHR in COPD. AHR is thought to occur as a result of variable and

fixed components. The variable components largely derive from the acute release

of pro-inflammatory mediators, while the persistent components result from

structural changes in the airways (1). Thus, to exclude the effects of structural

changes which develop following chronic smoke exposure in mice, we utilised a

mouse model of acute cigarette smoke exposure to determine whether RAGE

and/or TLR4 signalling promotes AHR in COPD.

71

MATERIALS AND METHODS

Mouse model of acute smoke exposure

Male C57BL/6 mice at 8-11 weeks of age were purchased from the Animal

Resource Centre (Perth, Australia). TLR4-/-, RAGE-/- and TLR4/RAGE-/- mice on

a C57BL/6 background were bred in the animal facility at the University of

Technology Sydney. All mice were housed under specific pathogen-free

conditions in groups of 4-5 per cage and maintained at 20-22oC on a 12-hour

day-night cycle. Food and water were supplied ad libitum. A whole body smoke

exposure chamber equipped with an air circulating fume hood was used

(InExpose, SCIREQ). Mice were exposed to a 2-sec computer controlled puff of

cigarette smoke (commercial Winfield Red Cigarettes, containing < 16 mg tar, <

1.2 mg nicotine and < 15 mg carbon monoxide) or fresh air every 30 seconds,

followed by 28 seconds of fresh air, three times a day for 4 days. Mice were

acclimatized to the chamber by exposing them to fresh air 3 times a day for 2

days prior to the start of the experiment. Serum cotinine levels after the final

smoke exposure session on day 4 were measured in samples from a subgroup

of wild-type mice using a commercial ELISA (Calbiotech). The significantly higher

cotinine levels of 72.33 ± 8.15 (n=4) when compared to fresh air controls 3.56 ±

1.23 (n=4) confirm effective smoke delivery. All procedures were performed at

the University of Technology Sydney under protocols compliant with the

Australian Code for the Care and Use of Animals for Scientific Purposes and

approved by the University of Technology Sydney Animal Care and Ethics

Committee.

72

Assessment of airway reactivity in vivo

Airway reactivity to methacholine was measured 18 h after the final smoke

exposure session on day 4 by the forced oscillation technique using the FlexiVent

apparatus (SCIREQ, Montreal, Canada). Mice were anesthetized using a cocktail

of xylazine (0.2mg/10g) and ketamine (0.4mg/10g body weight). An 18-gauge

blunt needle was inserted into the trachea and mice were kept under mechanical

ventilation at 200 breaths/min with a delivered tidal volume of 0.25 mL against a

positive end-expiratory pressure (PEEP) of 3 cm H2O. Total lung resistance (Rrs),

compliance (Crs) and elastance (Ers), proximal airway resistance (Rn) and distal

airway dampening (G) and elastance (H) were determined during administration

of increasing doses of nebulized methacholine (0 to 40 mg/mL) (Sigma-Aldrich,

St Louis, MO, USA).

Assessment of airway inflammation

Mice were exsanguinated after an overdose of pentobarbital (100mg/kg)

delivered immediately after in vivo assessment of airway reactivity. The lungs

were lavaged twice with 0.5 mL sterile Hanks Balanced Salt Solution (HBSS).

The collected bronchoalveolar lavage fluid (BALF) was spun at 3000 rpm for 10

min at 4oC. Cell supernatants were retained for analysis of cytokine/chemokine

expression, while cell pellets were resuspended in sterile HBSS for enumeration

of total and differential cell counts. To perform differential cell counts, cells were

spun on glass slides using a Cytospin 4 Cytocentrifuge (Thermo Fisher Scientific)

and were stained with Diff-Quik®. A total of 200 cells were counted for the

differential leukocyte count. The concentration of different cytokines and

chemokines in BALF were determined using a customized Magnetic Luminex

73

assay (R&D systems) using the MAGPIX® System. Five parameter logistic

regression of standard curves was performed to determine the concentration of

unknown samples.

Assessment of small airway reactivity using precision cut lung slices

Using separate groups of mice, precision cut lung slices (PCLS) were prepared

24 h after the final smoke exposure session on day 4 as previously described

(24, 25). Mice were killed by an overdose of pentobarbital (100mg/kg) before the

trachea was cannulated. Lungs were then inflated with ~1.4 mL of ultra-pure low

melting point agarose (2% wt/vol in HBSS /HEPES) followed by 0.4 mL of air to

push the agarose through to the alveolar spaces. Lungs were cooled to allow the

agarose to solidify, then removed and transferred to cold HBSS and stored at 4oC

overnight. Lobes were cut into 200 μm thick slices using a vibratome and

incubated in Dulbecco’s Modified Eagle Medium (DMEM, Gibco, with 4.5 g/l

glucose, L-glutamine, 110 mg/L sodium pyruvate) supplemented with 1%

penicillin-streptomycin (Gibco) at 37°C and 5% CO2 in 24-well plates overnight.

All experiments were performed at room temperature using custom-made

chambers. PCLS were mounted on a glass coverslip on a perspex support under

a piece of fine wire mesh, with a hole cut to allow visualization of a single airway

(approx 300 μm diameter). Silicon grease was applied in two parallel lines along

the mesh and an additional coverslip used to secure the PCLS and to create a

perfusion chamber. Drugs were delivered under gravity using a controlled valve

syringe system and drained under vacuum. Airways were observed under phase

contrast microscopy, using beating airway cilia to establish viability. Images were

74

captured and analysed using Video Savant and Image J software. Contraction to

MCh was measured as changes in airway lumen area, normalised to the initial

area during perfusion with HBSS alone.

Statistical analysis

Data were expressed as mean ± SEM and analysed using GraphPad Prism 7.

For analysis of differential cell counts and mediator release in BALF, multiple

group comparisons were made using one-way ANOVA and post hoc comparison

using the Bonferroni test. Two-way ANOVA was conducted to compare in vivo

MCh dose-response relationships with Bonferroni post-hoc analysis of individual

doses. MCh concentration-response curves from PCLS experiments were fitted

to calculate the pEC50 and maximum response and values for different groups

compared by one-way ANOVA. Data was considered significant with p-value less

than 0.05.

RESULTS

RAGE, but not TLR4, mediates acute smoke-induced airway inflammation

in mice.

To investigate whether RAGE and TLR4 co-operate in the initial inflammatory

response to acute smoke exposure, we exposed wildtype (WT), TLR4-/-, RAGE-/-

and TLR4/RAGE-/- mice to either fresh air (FA) or cigarette smoke (CS) from 3

cigarettes three times a day for 4 days. This protocol elicited a 2-fold increase in

total inflammatory cells in WT mice, that could be almost completely attributed to

the increase in the number of neutrophils 24 h post smoke exposure, similar to

previous studies (26) (Fig 2.1A). It also led to a significant increase in S100A8

75

and CCL3 protein levels in BALF, as well as a trend towards increased levels of

CXCL1 (Fig 2.1B). We also measured TNF-α, IL-6, IL-17A and IL-17E protein

levels, however these were not detected (data not shown).

RAGE-/- mice were protected against acute smoke-induced inflammation. This

was evidenced by significantly reduced numbers of infiltrating neutrophils, and

marked attenuation in BALF levels of both S100A8 and CCL3 compared to wild-

type mice (Fig 2.1A, B). Surprisingly, reduced airway neutrophilia in RAGE-/- mice

was not associated with reduced levels of CXCL1. Notably, TLR4-/- and

TLR4/RAGE-/- mice were not significantly protected against airway neutrophilia

or inflammatory mediator release in the BALF (Fig 2.1A, B).

(Figure 2.1, to be continued on the next page)

W T R AG E - /- T L R 4 - /- T L R 4 /R AG E - /-0

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76

Figure 2.1: RAGE, but not TLR4, mediates acute smoke-induced airway inflammation in mice. WT, RAGE-/-, TLR4-/- and TLR4/RAGE-/- mice were exposed to either fresh air (FA) or cigarette smoke (CS) from 3 cigarettes 3 times a day for 4 days. (A) Total and neutrophil cell counts in BALF. (B) S100A8, CCL3 and CXCL1 protein concentrations in BALF. Data represent mean ± SEM ****P < 0.0001 vs respective fresh air exposed mice. #P < 0.05, and ##P < 0.01 vs cigarette smoke exposed WT mice. N = 5-8 mice per group.

RAGE, but not TLR4, mediates acute smoke-induced airway hyperreactivity

in mice.

The contributions of RAGE and/or TLR4 to functional changes associated with

the airway inflammatory response to acute smoke exposure were also assessed.

There was no difference in any of the in vivo lung function parameters measured

at baseline prior to MCh administration in WT, RAGE-/-, TLR4-/- or TLR4/RAGE-/-

mice. Notably, however, in the fresh air groups, the increases in Rrs, Ers and G

in response to MCh were approximately 50% greater in RAGE-/- and TLR4-/- mice

B


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77

than in WT mice, indicating that RAGE and TLR4 inherently regulate airway

reactivity (Fig 2.2A, C; 2.3A, C; 2.4A, C). Although the increases in Rrs, Ers and

G in response to MCh tended to be greater in TLR4/RAGE-/- mice than WT mice,

they were not significantly increased. Changes in Crs, Rn and H with increasing

MCh were similar between all groups (data not shown).

Acute cigarette smoke exposure induced AHR to MCh, as indicated by significant

increases in Rrs, Ers and G in WT mice relative to their fresh air controls (Fig

2.2B,C; 2.3B,C; 2.4B,C). Although responses to MCh were greater in RAGE-/- air-

exposed mice than in WT air-exposed mice (Fig 2.2A, C; 2.3A, C; 2.4A, C), they

were protected from further increases in Rrs, Ers and G following acute smoke

exposure. For TLR4-/- mice, MCh-induced increases in all these parameters were

further elevated with smoke exposure, while only Rrs was elevated in

TLR4/RAGE-/- mice (Fig 2.2B,C; 2.3B,C; 2.4B,C).

78

Figure 2.2: RAGE, but not TLR4, mediates acute smoke-induced increases in total lung resistance. WT, RAGE-/-, TLR4-/- and TLR4/RAGE-/- mice were exposed to either fresh air (FA) or cigarette smoke (CS) from 3 cigarettes 3 times a day for 4 days. (A) Comparison of total lung resistance (Rrs) in all four strains after exposure to fresh air. (B) Total lung resistance (Rrs) and (C) Maximal increase in total lung resistance (Rrs) following exposure to fresh air or cigarette smoke. Data represent mean ± SEM. δP < 0.05, δδP < 0.05 vs fresh air exposed WT mice *P

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79

< 0.05, **P < 0.01, ***P < 0.001 vs respective FA exposed mice. #P < 0.05, ##P < 0.01 vs cigarette smoke exposed WT mice. N = 6-10 mice per group.

Figure 2.3: RAGE, but not TLR4, mediates acute smoke-induced increases in tissue airway dampening. WT, RAGE-/-, TLR4-/- and TLR4/RAGE-/- mice were exposed to either fresh air (FA) or cigarette smoke (CS) from 3 cigarettes 3 times a day for 4 days. (A) Comparison of tissue dampening (G) in all four strains after exposure to fresh air. (B) Tissue dampening (G) and (C) Maximal increase in tissue dampening (G) following exposure to fresh air or cigarette smoke. Data represent mean ± SEM. δδP < .01 vs WT-FA mice *P < .05, **P < .01 vs respective fresh air exposed

B a s e lin e 0 1 .2 5 2 .5 5 1 0 2 0 4 00

5

1 0

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G c

mH

2O.s

/mL

* *

B a s e lin e 0 1 .2 5 2 .5 5 1 0 2 0 4 00

5

1 0

1 5

2 0

M C h m g /m L

G c

mH

2O.s

/mL

B a s e lin e 0 1 .2 5 2 .5 5 1 0 2 0 4 00

1 0

2 0

3 0

M C h m g /m L

G c

mH

2O.s

/mL

*

B a s e lin e 0 1 .2 5 2 .5 5 1 0 2 0 4 00

5

1 0

1 5

2 0

M C h m g /m L

G c

mH

2O.s

/mL


1 0

2 0

3 0

G a

t Max

imal

MC

h re

spon

se

*

* *##

δ δ

δ δ

W T - F A

R A G E -/- - F A

TLR 4 -/ - - F A

T L R 4 /R A G E -/- - F A

F A

C S

W T - F A

W T - C S

R A G E -/-- F A

R A G E -/-- C S

TLR 4 -/ -- F A

TLR 4 -/ -- C S

T L R 4 /R A G E -/-- F A

T L R 4 /R A G E -/-- C S

80

mice. #P < .05, ##P < .01 vs cigarette smoke exposed WT mice. N = 6-10 mice per group.

W T - F A

R A G E -/- - F A

TLR 4 -/ - - F A

T L R 4 /R A G E -/- - F A

B a s e lin e 0 1 .2 5 2 .5 5 1 0 2 0 4 00

2 0

4 0

6 0

8 0

M C h m g /m L

Ers

cm

H2

O.s

/mL

δδ

B a s e lin e 0 1 .2 5 2 .5 5 1 0 2 0 4 00

2 0

4 0

6 0

8 0

M C h m g /m L

Ers

cm

H2

O.s

/mL

*

B a s e lin e 0 1 .2 5 2 .5 5 1 0 2 0 4 00

2 0

4 0

6 0

8 0

M C h m g /m L

Ers

cm

H2

O.s

/mL

B a s e lin e 0 1 .2 5 2 .5 5 1 0 2 0 4 00

4 0

8 0

1 2 0

M C h m g /m L

Ers

cm

H2

O.s

/mL

* *

B a s e lin e 0 1 .2 5 2 .5 5 1 0 2 0 4 00

2 0

4 0

6 0

8 0

M C h m g /m L

Ers

cm

H2

O.s

/mL


4 0

8 0

1 2 0

Ers

at

ma

xim

al M

Ch

re

spo

nse

*

* *##

δ δ

F A

C S

W T - F A

W T - C S

R A G E -/-- F A

R A G E -/-- C S

TLR 4 -/ -- F A

TLR 4 -/ -- C S

T L R 4 /R A G E -/-- F A

T L R 4 /R A G E -/-- C S

81

Figure 2.4: RAGE, but not TLR4, mediates acute smoke-induced increases in total elastance. WT, RAGE-/-, TLR4-/- and TLR4/RAGE-/- mice were exposed to either fresh air (FA) or cigarette smoke (CS) from 3 cigarettes 3 times a day for 4 days. (A) Comparison of total elastance (E) in all four strains after exposure to fresh air. (B) Total elastance (E) and (C) Maximal increase in total elastance (E) following exposure to fresh air or cigarette smoke. Data represent mean ± SEM. δP < .05 vs respective FA exposed mice *P < .05, **P < .01 vs respective FA groups. #P < .05, ##P < .01 vs cigarette smoke exposed WT mice. N = 6-10 mice per group. Assesment of small airway reactivity in smoke exposed mice

We have previously shown that acute smoke exposure in vivo modulates small

airway reactivity to contractile stimuli in mouse precision cut lung slices (PCLS)

ex vivo (25). Thus, we extended our studies to determine whether loss of RAGE

and/or TLR4 also alters smoke-induced changes in small airway reactivity ex

vivo.

Although air-exposed TLR4-/- and RAGE-/- mice exhibited enhanced airway

reactivity to MCh relative to WT mice in vivo, this inherent AHR was not reflected

in the small airways ex vivo. The contractile responses to MCh in PCLS from air-

exposed RAGE-/-, TLR4-/- and TLR4/RAGE-/- mice were comparable to air-

exposed WT mice, with maximum reductions in airway area of 40-50% (Fig 5A).

In vitro responsiveness to MCh in PCLS from WT was significantly attenuated

rather than increased following acute smoke exposure. The maximum reduction

in airway area of 50% was reduced by approximately 20% in PCLS from smoke-

exposed WT mice (Fig 5B). However, there were no differences in small airway

contractility to MCh in PCLS from smoke-exposed RAGE-/-, TLR4-/- and

TLR4/RAGE-/- mice compared to their matched air-exposed groups (Fig 5C-E).

82

Figure 2.5: RAGE and TLR4 do not mediate cigarette-smoke induced changes in small airway reactivity. WT, RAGE-/-, TLR4-/- and TLR4/RAGE-/- mice were exposed to either fresh air (FA) or cigarette smoke (CS) from 3 cigarettes 3 times a day for 4 days. (A) Airway contraction expressed as % initial airway lumen area in all four strains w exposure to fresh air only. (B) Airway contraction expressed as % initial airway lumen area in individual strains exposed to fresh air or cigarette smoke.

W T - F A

R A G E -/- - F A

TLR 4 -/ - - F A

T L R 4 /R A G E -/- - F A

-8 -7 -60

2 5

5 0

7 5

1 0 0

[M C h ] ( lo g M )

Air

wa

y lu

me

n a

rea

(% in

itia

l)

- 8 - 7 - 6

0

2 5

5 0

7 5

1 0 0

[ M C h ] ( l o g M )

Air

wa

y l

um

en

are

a (

% i

nit

ial)

*

- 8 - 7 - 6

0

2 5

5 0

7 5

1 0 0

[ M C h ] ( l o g M )

Air

wa

y l

um

en

are

a (

% i

nit

ial)

- 8 - 7 - 6

0

2 5

5 0

7 5

1 0 0

[ M C h ] ( l o g M )

Air

wa

y l

um

en

are

a (

% i

nit

ial)

- 8 - 7 - 6

0

2 5

5 0

7 5

1 0 0

[ M C h ] ( l o g M )

Air

wa

y l

um

en

are

a (

% i

nit

ial)

W T - F A

W T - C S

R A G E -/-- F A

R A G E -/-- C S

TLR 4 -/ -- F A

TLR 4 -/ -- C S

T L R 4 /R A G E -/-- F A

T L R 4 /R A G E -/-- C S

83

DISCUSSION

In this study, we demonstrate that RAGE and TLR4 differentially modulate airway

reactivity to acute cigarette smoke exposure in mice. We show that loss of RAGE

signalling is protective against cigarette smoke induced AHR to methacholine in

vivo, and that this effect is associated with reduced neutrophilic airway

inflammation. In contrast, loss of TLR4 signalling exacerbates AHR without

influencing the magnitude of the airway inflammatory response. These findings

provide unique insights into possible mechanisms of AHR in COPD and further

substantiate RAGE as a therapeutic target in this disease.

We found that in the absence of cigarette smoke exposure, RAGE and TLR4

gene-deficient mice exhibited a greater degree of airway reactivity to

methacholine in vivo compared to their wild-type counterparts, without any

evidence of increased airway inflammation. These findings are consistent with a

previous study by Milutinovic and colleagues which also reported inherent airway

reactivity in air-exposed RAGE gene-deficient mice (27). Abberrant expression of

RAGE in the lung is associated with abnormal lung morphogenesis, airspace

enlargement and the development of emphysema-like pathology (5, 28-32).

Moreover, it has been shown that TLR4 gene-deficient mice develop emphysema

as they age, largely as a result of increased oxidant generation and elastolytic

activity (33, 34). RAGE and TLR4 thus have an important role in maintaining lung

homeostasis, structure and function. Indeed, given the observation that AHR

precedes the development of COPD-like symptoms in the general population

(35), it is possible to speculate that altered or dysregulated expression of these

receptors may underlie the development of COPD in susceptible individuals.

84

Consistent with previous studies, our results suggest that RAGE mediates airway

neutrophilia in response to acute smoke exposure (4-8) and have further

demonstrated this effect is associated with concomittant induction of AHR, since

RAGE deficiency was protective against both of these outcomes. Our finding that

TLR4 gene-deficient mice were not protected against acute cigarette-smoke

induced airway neutrophilia contrasts with a similar acute exposure study by Doz

et al. (18). However, a recent study by Haw et al. (36) also showed that TLR4

gene-deficient mice were not protected against airway inflammation induced by

chronic cigarette smoke exposure. This latter study, together with our findings

here, suggest that RAGE plays a more dominant role than TLR4 in the airway

inflammatory response to cigarette smoke exposure.

Moreover, we found that RAGE and TLR4 signalling is associated with distinct

and opposing effects on AHR in the context of acute smoke exposure. Indeed,

while our findings suggest that RAGE gene-deficient mice were protected against

AHR as a result of reduced cigarette smoke-induced neutrophil infiltration, TLR4

gene-deficient mice had worse cigarette smoke-induced AHR even though they

didn’t have a further increase in neutrophils. It has been shown that TLR4 acts

as a tonic suppressor of the NADPH oxidase enzyme Nox3 in lung endothelial

cells, and that loss of TLR4 leads to a profound increase in lung oxidant

generation in the absence of overt lung inflammation (33, 34). So the additional

factor contributing to increased AHR in the absence of any further increase in

airway neutrophilic inflammation in TLR4 gene-deficient mice might be the

increased oxidants due to loss of suppression of Nox3. In contrast, RAGE

signalling leads to activation of the NADPH oxidase system (2), thus protection

85

against AHR and neutrophilic inflammation in RAGE gene-deficient mice may

also be due to a lower oxidant burden. The divergent effect of RAGE and TLR4

on NADPH oxidase may contribute to the loss of protection against AHR and

neutrophilic inflammation in RAGE/TLR4 deficient mice. Irrespective of the

underlying molecular mechanisms, however, our findings suggest that TLR4

inhibition may be detrimental in COPD, while RAGE inhibition is likely to afford

protection aganist multiple phenotypic traits.

Small airways are a major site of disease pathology in COPD (1). The application

of the PCLS technique has provided evidence of altered contractile responses

and signalling associated with acute cigarette smoke exposure in vivo in mice

(25). In addition, small airway contraction was also increased after ex vivo

treatment of mouse PCLS with elastase to induce emphysematous-like changes

(37-39) Thus, we extended our studies to determine whether the differences in

reactivity to MCh in vivo associated with RAGE and/or TLR4 gene deletion were

also evident in small airways ex vivo. We initially showed that contraction to MCh

was similar in PCLS from all air-exposed mice, suggesting that any structural

changes in the airways or surrounding parenchyma associated with deficiency of

RAGE and/or TLR4 that might contribute to in vivo AHR in the absence of

inflammation may be too subtle to be detectable in individual small airways.

Despite causing in vivo AHR, acute smoke exposure was associated with a

significant reduction in small airway reactivity in PCLS from wild-type mice and

no difference in PCLS from RAGE, TLR4 and RAGE/TLR4 gene-deficient mice

relative to their matched air-exposed groups. Since RAGE gene-deficient mice

86

were protected against both cigarette smoke-induced neutrophilia and in vivo

AHR, and in vitro contraction to MCh was unchanged, the persistent influence of

neutrophilic inflammation, as occurs in vivo, appears to be required to increase

airway contraction.

We have yet to define the mechanism for the unexpected decrease in contraction

in PCLS from wild-type mice and why it is abrogated in TLR4 and RAGE/TLR4

gene-deficient mice which had similar neutrophilia but relatively higher in vivo

AHR after acute smoke exposure. Of note, a recent study examined PCLS from

a guinea pig model of COPD in which 12 weeks LPS exposure induced

significantly increased alveolar airspaces. The increased small airway contraction

to MCh after LPS was consistent with results comparing PCLS from COPD

patients with non-COPD controls(40) . This suggests that gross structural

changes established in response to chronic inflammation in vivo can influence

small airway reactivity in vitro. Given the considerable evidence of altered

expression of RAGE and TLR4 in COPD, extending the current study to a chronic

smoke exposure model is likely to provide additional mechanistic insights on the

potentially complex interplay between RAGE and TLR4 signaling, structural

changes and AHR.

The current study has increased our understanding of relative contributions of

RAGE and TLR4 signaling to acute inflammation and AHR relevant to the initation

of COPD. Moreover, while previous studies have utilised RAGE and TLR4 gene-

deficient mice to study the individual role of these receptors in COPD-related

pathology, this is the first study to examine the combined effect of RAGE and

87

TLR4 gene deletion on the pulmonary response to acute cigarette smoke

exposure. Using this approach, it has been possible to directly compare the role

of each of these receptors in acute airway inflammation and changes in airway

reactivity. Intriguingly, while RAGE and TLR4 share some common ligands and

downstream signalling, our findings expose distinct and differential effects of

these receptor pathways in regulating airway inflammatory and functional

changes associated with COPD. Together, our findings following acute cigarette

exposure suggest that further investigation of the role of RAGE in COPD

pathogenesis are warranted and that RAGE rather than TLR4 should be pursued

as a therapeutic target in COPD.

88

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94

Chapter 3

DUAL ROLE OF RAGE AND TLR4 SIGNALING IN

SEVERE ASTHMA

95

INTRODUCTION

Asthma is a chronic airway disease associated with aberrant activation of innate

immune pathways at the airway mucosal surface. While many innate immune

receptors are implicated in asthma pathogenesis, a substantial body of evidence

suggests a critical role for toll-like receptor 4 (TLR4), one of the major pattern-

recognition receptors involved in the host immune response to tissue injury and

infection (1). Using experimental mouse models, we and others have shown that

activation of TLR4 signaling by environmental allergens and pollutants instructs

the activation of type 2 and type 17 immune responses involved in the

development of the asthmatic response (2-5).

The receptor for advanced glycation end products (RAGE) is a member of the

immunoglobulin superfamily of cell surface receptors. It has the capacity to

interact with a diverse repertoire of endogenous ligands and is an important

mediator of the allergic asthmatic response (5-9). Importantly, our recent studies

indicated that while TLR4 is involved in the initial activation of the immune

response to inhaled allergens, subsequent activation of RAGE appears to be

required for the amplification and propagation of the airway immune response

that leads to asthma. Moreover, we found that TLR4, RAGE and TLR4/RAGE

gene-deficient mice were similarly protected against allergic asthma, suggesting

these receptors act at critical but sequential points in the allergic asthmatic

response, with interception of either point being sufficient for protection (5).

Importantly, however, TLR4 and RAGE have been shown to function in a

synergistic manner under certain conditions. For example HMGB1 is an

96

endogenous protein that signals via TLR4 and RAGE and has been shown to

enhance TLR4-dependent LPS responses in macrophages by promoting the

phosphorylation of MAPK p38 and by the activation of NF-κB through RAGE (10).

We have shown that HMGB1 is an important mediator of the innate immune

response in mouse models of allergic asthma (5). Moreover, others have reported

increased sputum levels of HMGB1 in patients with severe asthma compared

with healthy controls, but not patients with mild-moderate asthma (11). Thus while

we have previously established that TLR4 and RAGE act independently in the

airway immune response to inhaled allergens (5), we hypothesize that co-

operative signaling between these receptor pathways drives the inflammatory

response in severe asthma, a subtype of disease that is relatively resistant to

treatment with anti-inflammatory corticosteroids (12).

In this study we utilized TLR4, RAGE and TLR4/RAGE gene deficient mice to

examine possible co-operation between these receptors in a mouse model of

severe corticosteroid-resistant asthma (13). The reversible phosphorylation of

serine, threonine, and tyrosine residues directly controls many cellular processes,

thus we have also performed a global phosphoproteomic analysis of lung tissue

samples from these mice to identify signaling pathways activated down-stream

of TLR4 and RAGE ligation in severe asthma.

97


Mouse studies

Female C57BL/6 wild-type mice were purchased from the Australian Resource

Centre (Perth, Australia). C57BL/6 TLR4-/-, RAGE-/- and TLR4/RAGE-/- mice were

bred in the animal facility at the University of Technology Sydney. All mice were

housed under specific pathogen free conditions. At 8 weeks of age, mice were

sensitized to house dust mite (HDM) allergen (100μg) (Dermatophagoides

pteronyssinus, Greer Laboratories, Lenoir, NC, USA) emulsified with an equal

volume of complete Freund’s adjuvant (CFA) (Sigma-Aldrich, St Louis, MO, USA)

via subcutaneous injection. On day 14, mice were challenged with HDM (100μg)

intranasally. Control mice were sensitized and challenged with PBS only. All

procedures were performed at the University of Technology Sydney under

protocols compliant with the Australian Code for the Care and Use of Animals for

Scientific Purposes and approved by the University of Technology Sydney Animal

Care and Ethics Committee.

Airway hyperresponsiveness (AHR) was measured 24 h after allergen challenge

by the forced oscillation technique using the FlexiVent apparatus (SCIREQ,

Montreal, Canada). Briefly, mice were anesthetized using a cocktail of xylazine

(0.2mg/10gm) and ketamine (0.4mg/10gm body weight). An 18-gauge blunt

needle was inserted into the trachea and mice were kept under mechanical

ventilation at 200 breaths/min with a delivered tidal volume of 0.25 mL against a

positive end-expiratory pressure (PEEP) of 3 cm H2O. Total lung resistance (Rrs),

compliance (Crs) and elastance (Ers), proximal airway resistance (Rn), distal

airway dampening (G) and distal airway elastance (H) were determined at

98

baseline and in response to increasing doses of nebulized methacholine up to 10

mg/mL (Sigma-Aldrich, St Louis, MO, USA).

Once lung function measurements were completed, mice were exsanguinated

with an overdose of pentobarbital (100mg/kg). The lungs were lavaged twice with

0.5 mL sterile Hanks Balanced Salt Solution (HBSS). The collected fluid was spun

at 3000 rpm for 10 min at 4oC. Cell supernatants were retained for analysis of

cytokine/chemokine secretion, while cell pellets were resuspended in sterile

HBSS for enumeration of total and differential cell counts. To perform differential

cell counts, cells were spun on glass slides using a Cytospin 4 Cytocentrifuge

(Thermo Fisher Scientific) and were stained with Diff-Quik®. A total of 200 cells

were counted.

Lung protein digestion and phosphopeptide enrichment

We performed quantitative phosphoproteomic analysis on lung tissue obtained

from a subset (N=5) of PBS and HDM challenged WT, TLR4-/-, RAGE-/- and

TLR4/RAGE-/- mice studied above. The flash frozen right lung lobe was lysed

using RIPA buffer containing protease (cOmplete™ ULTRA Roche) and

phosphatase inhibitors (PhosSTOP™, Roche). The protein concentration was

determined using the BCA protein assay (Pierce™ BCA Protein Assay Kit). 300

µg of total protein from each sample was digested overnight using trypsin after

performing the reduction and alkylation process. The digested peptides were

cleaned up using the C18 column (Oasis HLB Light 1 mL cartridge). The cleaned

and digested peptides were then subjected to phosphopeptide enrichment using

the Titansphere Phos-TiO Kit (GL-Science) according to the manufacturer

99

instructions. Briefly, the dried peptides from each sample were dissolved in 150

μL of binding buffer. TiO2 beads were washed twice with washing buffer and a

total of 1 mg of tryptic peptides solution was incubated with an appropriate

amount (tryptic peptide: TiO2 = 1:1, w/w) of TiO2 beads by end-over-end rotation

at room temperature for 30 min. The phosphopeptide-bound beads were

collected by brief centrifugation, washed twice with 500 μL washing buffer and

transferred to a C18 column placed on the top of a 1.5 mL centrifuge tube. The

StageTip was centrifuged to remove the wash buffer completely and

phosphopeptides were collected from the resin with elution buffer.

LC-MS/MS analysis

The digested peptides were separated by nanoLC using an Ultimate nanoRSLC

UPLC and autosampler system (Dionex, Amsterdam, Netherlands). Briefly,

samples of 2.5 µL volume were concentrated and desalted onto a micro C18 pre-

column (300 µm x 5 mm, Dionex) with H2O:CH3CN (98:2, 0.1 % TFA) at 15

µL/min. After washing for 4 minutes, the pre-column was switched (Valco 10 port

UPLC valve, Valco, Houston, TX) into line with a fritless nano column (75µ x

~15cm) containing C18AQ media (1.9µ, 120 Å Dr Maisch, Ammerbuch-Entringen

Germany). The peptides were eluted using a linear gradient of H2O:CH3CN

(98:2, 0.1 % formic acid) to H2O:CH3CN (64:36, 0.1 % formic acid) at 200 nL/min

over 30 min. A high voltage of 2000 V was applied to low volume Titanium union

(Valco) and the tip was positioned ~ 0.5 cm from the heated capillary (T=275°C)

of an Orbitrap Fusion Lumos (Thermo Electron, Bremen, Germany) mass

spectrometer. The positive ions were generated by electrospray and the Fusion

Lumos operated in data dependent acquisition mode (DDA).

100

A survey scan m/z 350-1750 was acquired in the orbitrap (resolution = 120,000

at m/z 200, with an accumulation target value of 400,000 ions) and lockmass

enabled (m/z 445.12003). Data-dependent tandem MS analysis was performed

using a top-speed approach (cycle time of 2s). MS2 spectra were fragmented by

HCD (NCE=30) activation mode and the ion-trap was selected as the mass

analyzer. The intensity threshold for fragmentation was set to 25,000. A dynamic

exclusion of 20 s was applied with a mass tolerance of 10ppm.

Data Processing

The raw mass spectrometric data were analyzed using MaxQuant (version 1.52).

The MS/MS spectra were matched against the mouse Uniprot FASTA database

v.4/18/2018. The enzyme specificity was set to trypsin, and the search included

the cysteine carbamidomethylation as a fixed modification and N-acetylation of

protein, oxidation of methionine, and/or phosphorylation of Ser, Thr, Tyr residue

(STY) as variable modifications. Up to two missed cleavages were allowed for

protease digestion and peptides had to be fully tryptic. The phosphopeptides,

proteins, and phosphorylation-site identifications were filtered based on a 1%

false discovery rate threshold based on searching of the reverse sequence

database.

Bioinformatic analysis

Bioinformatic analysis was performed using the Perseus software (v 1.63)

environment. For the phosphoproteomic data, raw peptide-ion intensities were

extracted from the MaxQuant pSTY file. Only phosphosites with a localization

probability ≥ 0.75 (Class 1 Phosphosites) were included in the analysis. After data

101

filter for class I phosphosites, the quantitative values in two groups required at

four valid values of five x sample were then normalized by subtracting the median

of all the intensities in each sample. Imputation was then applied to fill missing

values. To determine significantly regulated phosphosites, a multiple sample test

(ANOVA) was applied and a p-value of 0.01 was set as the threshold to determine

significance between the groups. For the hierarchical clustering analysis, log

values of the signal intensity of each phosphopeptide profile were determined

after z-score normalization of the data within Euclidean. Functional analysis for

gene ontology (GO) enrichment was performed using the PantherDB

bioinformatics tool. Protein-protein interaction network analysis was performed

using with the STRING database (version 10.5) with a confidence cutoff of 0.4.

In the resulting protein association network, proteins are presented as nodes

which are connected by lines whose thickness represents the confidence level

(0.6–0.9). KEGG pathway enrichment analyses were implemented with the

DAVID bioinformatics tool.

Kinase activity prediction

Phosphopeptide sequences with associated extracted intensities of the WT,

RAGE-/-, TLR4-/- and TLR4/RAGE-/- mice and those that were significantly

upregulated in the HDM challenged groups (P < 0.05) were searched for

consensus sequences using the Motif-X algorithm. Central residues were set as

S or T with the “MS/MS” foreground format searched against the whole mouse

proteome. Window width was set to 13 and the cutoff for minimal occurrences in

the searched phosphopeptide sequences was set to 20. Significance was set to

0.000001. Identified consensus sequences were then searched for the cognate

102

kinases known to target these sequences using the PhosphoMotif Finder that

predicts the kinase-substrate relationships.

Statistical Analysis

Data were expressed as mean ± SEM and analysed using GraphPad Prism 7.

For analysis of differential cell counts and mediator release in BALF, multiple

group comparisons were made using one-way ANOVA and post hoc comparison

using the Bonferroni test. Two-way ANOVA was conducted to compare in vivo

MCh dose-response relationships with Bonferroni post-hoc analysis of individual

doses. For analysis of protein phosphorylation signal intensity, multiple group

comparisons were made using two-way ANOVA and post-hoc comparison using

the Tukey’s test. Data was considered significant with p-value less than 0.05.

RESULTS

Combined deletion of RAGE and TLR4 protects against airway

inflammation and airway hyperresponsiveness in severe experimental

asthma

To determine whether TLR4 and RAGE signaling, either alone or in co-operation,

contributes to airway inflammation and abnormal airway function in severe

asthma, we used a mouse model of severe experimental asthma in which WT,

RAGE-/-, TLR4-/-, and TLR4-/-/RAGE-/- mice were sensitized with HDM in the

presence of complete Freund’s adjuvant and then 14 days later challenged with

a single dose of HDM. This protocol elicited significant release of inflammatory

mediators and infiltration of inflammatory cells into the airway lumen of WT mice

which was almost completely attributed to the increase in the number of

103

neutrophils and eosinophils (Fig 3.1A – E, Fig 3.2A – E). It also elicited significant

induction of AHR (Fig 3.3A – F).

RAGE-/- and TLR4-/- mice were not protected against airway neutrophilia or

eosinophilia. However, combined deletion of both RAGE and TLR4 was

associated with a significant and marked reduction in airway neutrophil numbers

and approximately 50% reduction in airway eosinophil numbers, although this

was not statistically significant (Fig 3.1C, D). Consistent with these findings, we

observed significant inhibition of several pro-neutrophilic mediators including

S100A8, TNF-α CXCL1 and CCL3 and the pro-eosinophilic mediator CCL5 in the

BALF of TLR4/RAGE-/- mice. Interestingly, BALF levels of S100A8, TNF-α, CCL3

and CCL5 were also significantly attenuated in TLR4-/- mice, but not RAGE-/- mice

(Fig 3.2A – E). Protection against airway inflammation in TLR4/RAGE-/- mice was

accompanied by significant attenuation of AHR. This was in stark contrast to

RAGE-/- and TLR4-/- mice which exhibited significantly greater AHR than WT

control mice (Fig 3.3A – F). Together, these findings are the first to suggest that

RAGE and TLR4 act in a co-operative manner to drive airway inflammatory and

functional responses in severe experimental asthma.

104

Figure 3.1: Combined deletion of RAGE and TLR4 protects against granulocytic airway inflammation in severe experimental asthma. Total cell and differential cell counts in BALF. Data represent mean ± SEM. *P < 0.05, ***P < 0.001 vs respective PBS control; ##P < 0.01 vs HDM challenged WT mice. N = 10-11 mice per group

WT RAGE-/- TLR4-/- TLR4/RAGE-/-0

20

40

60To

tal

Cells

(x 1

04 /mL)

****

********

*


5

10

15

Mac

roph

ages

(x 1

04 /mL)

WT RAGE -/- TLR4 -/-TLR4/RAGE -/-0

2

4

6

8

Eosi

noph

ils (x

104 /m

L)

****

**** ****

WT RAGE -/- TLR4 -/-TLR4/RAGE -/-0.0

0.1

0.2

0.3

0.4

Lym

phoc

ytes

(x 1

04 /mL)

*

* *


10

20

30

40

Neu

troph

ils (x

104 /m

L)****

**** ****

##

PBSHDM

PBSHDM

PBSHDM

PBSHDM

PBSHDM

105

Figure 3.2: Combined deletion of RAGE and TLR4 protects against inflammatory mediator release in severe experimental asthma. Inflammatory mediators were measured in BALF by multiplex assay. Data represent mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 vs respective PBS control; #P < 0.05, ##P < 0.01 vs HDM challenged WT mice. N = 4-5 mice per group.


20000

40000

60000

80000S1

00A8

pg/

mL

******

** *# #


20

40

60

80

100

CXC

L1 p

g/m

L

***

***

##


20

40

60

80

100

CC

L3 p

g/m

L***

***

***

##


10

20

30

40

TNF-

α p

g/m

L

***

***

# #

WT RAGE -/- TLR4 -/- TLR4/RAGE-/-0

200

400

600

800

1000

CC

L5 p

g/m

L

******

** *# #

PBSHDM

PBSHDM

PBSHDM

PBSHDM

PBSHDM

106

Figure 3.3: Combined deletion of RAGE and TLR4 protects against airway hyperreactivity in severe experimental asthma. In vivo lung function parameters were measured by the forced oscillation technique using the FlexiVent apparatus. Data represent mean ± SEM. **P < 0.01 vs respective PBS control; #P < 0.05, ##P < 0.01 vs HDM challenged WT mice. N = 9-11 mice per group.

Impact of RAGE and/or TLR4 gene deletion on protein phosphorylation in

severe experimental asthma

To obtain an unbiased picture of the signaling pathways activated downstream of

RAGE and/or TLR4 ligation in severe experimental asthma, we performed global

phosphopeptide profiling on lung tissue isolated from a subset (N=5) of PBS and

HDM challenged WT, TLR4-/-, RAGE-/- and TLR4/RAGE-/- mice studied above.

We identified a total of 11916, 12936, 12655, 12377 phosphorylation sites on

Baseline 0 0.78 1.56 3.12 6.25 12.50.00

0.01

0.02

0.03

0.04

MCh mg/mL

Crs

cm

H2O

.s/m

L

**## ** **

Baseline 0 0.78 1.56 3.12 6.25 12.50

1

2

3

4

5

6

7

MCh (mg/mL)

Rrs

cm

H2O

.s/m

L

**

**

##

**##

##

Baseline 0 0.78 1.56 3.12 6.25 12.50

40

80

120

Mch mg/mL

Ers

cm

H2O

.s/m

L

****

##

##

##

**

Baseline 0 0.78 1.56 3.12 6.25 12.50.00

0.75

1.50

2.25

MCh mg/mL

Rn

cmH

2O.s

/mL

****

##

**

##

##

Baseline 0 0.78 1.56 3.12 6.25 12.50

5

10

15

20

25

30

MCh mg/mL

G c

mH

2O.s

/mL

**

**

##

**##

Baseline 0 0.78 1.56 3.12 6.25 12.50

30

60

90

Mch mg/mL

H c

mH

2O.s

/mL

**

##

**## **

WT - PBSWT - HDM

RAGE-/- - PBS

RAGE-/- - HDM

TLR4-/- - PBS

TLR4-/- - HDM

TLR4RAGE-/- - PBS

TLR4RAGE-/- - HDM

107

3220, 3451, 3299, 3241 distinct proteins in lung tissue samples obtained from

WT, TLR4-/-, RAGE-/- and TLR4/RAGE-/- mice, respectively. The number of

serine, threonine and tyrosine phosphorylation sites identified in PBS or HDM

challenged WT, TLR4-/-, RAGE-/- and TLR4/RAGE-/- mice are shown in Fig 3.4A

– D. We identified a total of 71, 10 and 138 phosphopeptides in lung tissue

samples obtained from WT, RAGE-/- and TLR4-/- mice, of which 61, 7 and 122

were hyper-phosphorylated in severe experimental asthma (i.e. HDM challenged

mice), respectively. We did not detect significant phosphorylation in lung tissue

samples obtained from TLR4/RAGE-/- mice (Fig 3.5A – D, Table 3.1).

Figure 3.4: Quanification of phosphorylated proteins in the lung in severe experimental asthma. Total counts of Ser, Thr, and Tyr residues within all peptides of phosphorylated proteins in lung tissue isolated from PBS and HDM challenged WT, RAGE-/-, TLR4-/-, TLR4/RAGE-/- mice. Data represent total counts derived from 5 lung tissue samples for each experimental group.

pSer pThr pTyr0

2000

4000

6000

Phos

phos

ites

Cou

nt

WT - PBSWT - HDM

pSer pThr pTyr0

2000

4000

6000

Phos

phos

ites

Cou

nt

RAGE-/- - PBSRAGE-/- - HDM

pSer pThr pTyr0

2000

4000

6000

Phos

phos

ites

Cou

nt

TLR4-/- - PBSTLR4-/- - HDM

pSer pThr pTyr0

2000

4000

6000

Phos

phos

ites

Cou

nt

TLR4/RAGE-/- - PBSTLR4/RAGE-/- - HDM

108

Figure 3.5: Volcano plot depicting differential phosphorylation of proteins in severe experimental asthma. Significant phosphorylation of proteins in response to PBS or HDM challenge in WT, RAGE-/-, TLR4-/-, TLR4/RAGE-/- mice are indicated above the line on the left and right hand side of the volcano plot, respectively. All ratios measured were median-normalised and log 2 transformed. A one sample t-test was performed where the null hypothesis was equal to 0. The statistical significance was –log 10 transformed (y-axis) and plotted against the t-test difference (x-axis).

A B

C D

HDMPBS HDMPBS

HDMPBS

WT RAGE-/-

TLR4-/- TLR4/RAGE-/-

HDMPBS

109

Table 3.1: Differentially phosphorylated proteins in response to PBS and HDM challenge in WT, RAGE-/- and TLR4-/- mice

WT PBS WT HDM RAGE-/-

PBS RAGE-/-

HDM TLR4-/- PBS TLR4-/- HDM

Pwp2 Phf2 Wdr44 Bclaf1 Ccar2 Cald1 Hcar2 Tppp Rcsd1 Kank4 Ccdc88b Ccdc94 Smn1 Morc3

Akap12 Tcof1 Atxn2l Lig1 Cdk16 Smn1 Hpca Eps8 Itih2

Hcar2 Srrm2 Lsp1 Eif3b

Sorbs1 Pinx1

Slk Ptrf Clk1 Dck Mphosph10 Nop56

Dnajc1 Slc9a1 Clk1 Gmip

Lrrc16a Hmha1

Samsn1 Cgnl1 Samsn1 Fam207a St3gal2 Nfkb2

Epb4 Ddx54 Pla2g4a

Efcc1 Pdcd11

Pard3 Lsp1 Abr Pdcd4 Sdad1

Arhgef28 Lsp1 Lsp1

Ddx21

Mapt Mcm3 Lig1

Bin2

Slc6a8 Nop56 Lig1 Gm13889

Thrap3 Ccdc88b Ptprc

Hist1h1c

Dennd5a Rnmt Top2b

Hist1h1d

Ptrf Mcm2 Top2b

Ahnak

Pdcd4 Tcof1 N4bp1

Nrarp

Mtss1l Lsp1 Fga

Nrarp

Cad Zeb2

Dock2

Kiaa1551 Fam21

Epsti1

Ncbp1 Ifnar2

Lcp1

Arhgap30 Lig1

Plcb4

Ahnak Hist1h1e

Plcb4

Tcea1 Rai14

Ccr1

Cdk11b Med24

Atrx

Cdk11b Mphosph8

Fbl

Ahnak Mphosph8

Gch1

Marcksl1 Eomes

Pram1

Ddx24 Ccdc86

Stat3

Wdhd1 Eif3b

Ifitm3

Ddx21 Junb

Hist1h1e

Cdk1 Acin1

Igf2r

Mcm2 Tmem176b

Ifit3

Rgs14 Hmha1

Samsn1

Znrf2 Junb

Apobr

Ptpn6 Ahnak

Gmip

Dlgap4 Ifitm3

Smarcad1

Bin2 Brpf1

Batf3

Dock2 Eif2ak2

110

Hbat1

Junb Zbp1

Ogfr

Hpca Junb

Igf2r

Ccdc88b Samsn1

Tox4

Eef1d Junb

Etv6

Spn Myo9b

Junb

Arid3a Tacc2

Hcar2

Hist1h1c Lmo7

Junb

Hist1h1d Junb

Dennd1a

Rcsd1 Fcgr1

Junb

Rcsd1 Arhgef11

Mybbp1a

Pram1 Rcsd1

Akt1

Raf1 Fbl

Junb

Apobr Gm12250

Junb

Lsp1 Marcks

Eif3b

Sp110 Mtcl1

Ahsg

Cd69 Skap2

Lrrfip1

Rcsd1 Ncf2

Ncf1

Ddx21 Ccr1

Zbp1

Akap11 Ifi204

Ifi204

Epsti1 Cast

Gm12250

Sp110 Ifi204

Ifi204

Arid5a Lrrfip1

Ncf2

Traf1 Arhgap17

Evaluation of the corresponding biological annotations revealed that the

phosphorylation patterns occurred on proteins linked to disparate subcellular

compartments. 71% of all phosphoproteins identified in all samples were

categorized as cell part, while 29% were categorized as organelle. Nuclear and

cytoskeletal proteins accounted for 53% and 19% of organelle proteins,

respectively, while mitochondrial and other organelle proteins accounted for 3-

5% each.

Gene Ontology analysis by molecular function and biological function indicated

that the majority of the 61 and 122 phosphosites identified in HDM challenged

WT and TLR4-/- mice, respectively (Table 3.1), had binding or catalytic activities

111

(Fig 3.6A), and were predominantly involved in cellular process and metabolic

process (Fig 3.6B, 3.6F). GO analysis by molecular function and biological

function for the 7 phosphosites identified in HDM challenged RAGE-/- mice (Table

3.1) is shown in Fig 3.6C and 3.6D, respectively, however, given the small

number of proteins identified, this data must be interpreted with caution.

Figure 3.6. Gene Ontology terms assigned to differentially upregulated phosphorylated proteins in severe experimental asthma. Gene Ontology analysis by molecular function (A, C, E) and biological function (B, D, F) for differentially upregulated phosphorylated proteins in HDM challenged WT, RAGE-/-, TLR4-/- mice. Data were analysed using PANTHER GO analysis. Impact of RAGE and/or TLR4 gene deletion on signaling pathways activated

in severe experimental asthma

To understand the down-stream signaling events that regulate RAGE and/or

TLR4 dependent responses in severe experimental asthma, we next used the

A

B

C

WT HDM

RAGE-/- HDM

TLR4-/- HDM

Molecular function Biological function

112

STRING database to generate a protein interaction network of the 61, 7 and

122 phosphosites identified in HDM challenged WT, RAGE-/- and TLR4-/- mice,

respectively (Table 3.1). STRING allows for the analyses of protein-protein

interactions of a given set of genes based on correlation with predicted and

experimental sources (14). Here, the STRING analysis revealed that 17 of the

61 (27.9 %) phosphosites identified in HDM challenged WT mice were

interconnected. Of these, 12 are involved in immune system activation, while 4

are involved in the response to LPS biological function (Fig 3.7B, Table 3.2).

STRING analysis also revealed functional links between 46 of the 122 (38%)

phosphosites identified in HDM challenged TLR4-/- mice (Fig 7D, Table 3.2). Of

these, 19 are involved in immune system activation and 39 are involved in the

regulation of metabolic process. This reasonably moderate degree of

connectivity among 122 phosphosites suggests that a sizeable number of the

HDM-regulated phosphosites potentially partake in the same protein complex

and possibly the same cellular signaling processes. No protein-protein

interactions were detected among the 7 phosphosites identified in HDM

challenged RAGE-/- mice, possibly due to the small number of proteins (data

not shown). Protein-protein interactions were also not detected among the 10,

3 and 16 phosphosites identified in PBS challenged WT (Fig 7A), RAGE-/- mice

(data not shown) and TLR4-/- mice (Fig 7C).

115

Table 3.2: Interconnected proteins identified in STRING analysis

WT HDM TLR4-/- HDM Immune system activation

Response to LPS biological function

Immune system activation

Regulation of metabolic process

Gch1 Ncf1 Ifnar2 Niacr1 Rnmt

Stat3 Akt1 Ptpn6 Ccr1 Tcea1

Lcp1 Junb Dock2 Ptpn6 Nop56

Akt1 Nfkb2 Ptprc Ifnar2 Fga

Ahnak Raf1 Spn Ddx24

Ncf1 Spn Pla2g4a Ddx54

Nfkb2 Cd69 Ncf2 Ddx21

Ifit3 Ccr1 Ptprc Cad

Zbp1 Hcar2 Ifi204 Top2b

Junb Ifi204 Zbp1 Brpf1

Batf3 Eif2ak2 Lrrfip1 Lig1

Dock2 Junb Epsti1 Wdhd1

Zbp1 Marcksl1 Mphosph8

Tcea1 Marcks Cdk11b

Fga Hcar2 Med24

Ncf2 Eif2ak2 Myo9b

Myo9b Eif3b Lmo7

Fcgr1 Ncbp1 Znrf2

Eomes Smn1 Lsp1

Raf1

To identify potential signaling pathways impacted by RAGE and/or TLR4 gene

deletion in severe experimental asthma, we also performed KEGG pathway

analysis on the 61, 7 and 122 phosphosites in HDM challenged WT, RAGE-/-

and TLR4-/- mice (Table 3.1). Phosphosites identified in HDM challenged WT

and TLR4-/- mice were significantly enriched in three separate KEGG pathways,

116

as shown in Table 1. Notably, the top enriched pathways in each case i.e. the

chemokine signaling pathway (depicted in Fig. 3.8) and Fc gamma R-mediated

phagocytosis pathway (depicted in Fig. 3.9) included phosphosites identified in

HDM challenged WT mice (Dock 2 and Akt1, see Fig 3.7B) and TLR4-/- mice

(fcgr1, see Fig 3.7D). Phosphosites identified in HDM challenged RAGE-/- mice

were not significantly enriched in KEGG pathways.

Figure 3.8: Chemokine signalling KEGG pathway. Differentially upregulated phosphorylated proteins identified in HDM challenged WT mice were significantly enriched in the chemokine signaling KEGG pathway determined using David 6.8. Red stars indicate specific differentially upregulated phosphorylated proteins identified in HDM challenged WT mice.

117

Figure 3.9: Fc gamma R-mediated phagocytosis KEGG pathway. Differentially upregulated phosphorylated proteins identified in HDM challenged TLR4-/- mice were significantly enriched in the Fc gamma R-mediated phagocytosis KEGG pathway determined using David 6.8. Red stars indicate specific differentially upregulated phosphorylated proteins identified in HDM challenged TLR4-/- mice. Table 3.3: Enriched KEGG pathway

Strain Enriched KEGG pathway in HDM challenged mice p value

WT Chemokine signaling pathway 7.4E-04

Osteoclast differentiation 1.4E-04

Epstein-Barr virus infection 8.0E-02

TLR4-/- Fc gamma R-mediated phagocytosis 7.5E-05

Herpes simplex infection 4.6E-03

Leishmaniasis 4.6E-03

118

Analyses of phosphorylation motifs and predicted kinases

The amino acids surrounding a phosphosite constitute important recognition

motifs for cognate kinases (15). To identify linear substrate kinase motifs,

sequence logos were constructed from the aligned amino acid sequences of the

61, 7 and 122 phosphosites identified in HDM challenged WT, RAGE-/-, and

TLR4-/- mice (Table 3.1) using the Motif-X algorithm. This analysis identified a

significantly (P < 0.0000001) enriched proline directed motif (…..SP…..) among

the regulated phosphoserine residues in HDM challenged WT and TLR4-/- mice

(Fig 3.10). Moreover, we identified an acidophilic motif containing a glutamine at

the +4 position of the central serine residue (…..S….E.) in the HDM challenged

TLR4-/- mice (Fig 3.10). Analysis of phosphosites identified in HDM challenged

RAGE-/- mice did not reveal any substrate motifs. Having identified the consensus

motifs, we then searched for the cognate kinases that target these motifs using

PhosphoMotif Finder, which predicts kinase-substrate relationships. This

analysis identified three kinases, namely GSK-3, ERK1/2 and CDK5 that target

the proline directed motif (…..SP….) in HDM challenged WT (Fig 3.10A) and

TLR4-/- mice (Fig 3.10B). It also identified Casein Kinase II which targets the

(…..S….E.) motif in HDM challenged TLR4-/- mice (Fig 3.10B).

119

Group Motif Kinase Motif Score

Matches Fold Increase

WT HDM .....SP….. GSK-3

ERK1/2

CDK5

6.36 31 2.69

TLR4-/-

HDM

.....SP….. GSK-3

ERK1/2

CDK5

13.19 60 2.92

…..S….E. CKII 7.31 38 2.63

Figure 3.10. Predicted kinase activity in severe experimental asthma. Kinase substrate motifs were constructed from the aligned amino acid sequences of differentially upregulated phosphorylated proteins in HDM challenged WT (upper panel) and TLR4-/- mice (lower panel) using the Motif-X algorithm. The cognate kinases that target these motifs were predicted using PhosphoMotif Finder, as indicated in the table.

WT HDM

TLR4-/- HDM

A

B

120

Impact of RAGE and/or TLR4 gene deletion on protein phosphorylation in

severe experimental asthma

Finally, to determine the impact of RAGE and/or TLR4 gene deletion on protein

phosphorylation in severe experimental asthma, we performed unsupervised

hierarchical clustering on all phosphorylated proteins identified in all experimental

groups (Fig 3.4A – D). This analysis identified 77 phosphorylated proteins that

were statistically up or down regulated across the different experimental groups

(Fig 3.11). Thus, we used the signal intensities for each of these 77

phosphorylated proteins to quantify the extent of phosphorylation in individual

samples. Notably, we identified 19 proteins that were significantly phosphorylated

in response to HDM challenge in WT, RAGE-/- and TLR4-/- mice, but not in

TLR4/RAGE-/- mice. Phosphorylation of these proteins are therefore likely to be

involved in mediating co-operative effects of TLR4 and RAGE signaling in severe

experimental asthma (Fig 3.12).

121

Figure 3.11. Impact of RAGE and/or TLR4 signaling on protein phosphorylation in severe experimental asthma. Unsupervised hierarchical clustering on all phosphorylated proteins identified in PBS and HDM challenged WT, RAGE-/-, TLR4-/- and TLR4/RAGE-/- mice was performed using Perseus 6.3. A multiple sample test (ANOVA) was performed using the log2 intensity values of significantly regulated phosphoproteins. The heat map depicts the intensity of 77 phosphorylated protein that were significantly up or down regulated across all experimental groups.

123

We also performed hierarchical clustering on phosphorylated proteins that were

identified in PBS/HDM challenged WT mice and each of the PBS/HDM-

challenged gene-deficient mice separately. This analysis identified 28 and 139

phosphorylated proteins that were statistically up or down regulated in WT vs

RAGE-/- mice (Fig 3.13) and WT vs TLR4-/- mice (Fig 3.14), respectively. As

above, we used the signal intensities for the individual phosphorylated proteins

to quantify the extent of phosphorylation in individual samples. Interestingly, this

analysis identified 2 and 11 proteins that were significantly more phosphorylated

in response to HDM challenge in RAGE-/- and TLR4-/- mice (Fig 3.15),

respectively, when compared to WT mice. Phosphorylation of these proteins may

explain why RAGE-/- and TLR4-/- mice are more hyperreactive than WT mice.

124

Figure 3.13: Impact of RAGE signaling on protein phosphorylation in severe experimental asthma. Unsupervised hierarchical clustering on all phosphorylated proteins identified in PBS and HDM challenged WT and RAGE-/- mice was performed using Perseus 6.3. A multiple sample test (ANOVA) was performed using the log2 intensity values of significantly regulated phosphoproteins. The heat map depicts the intensity of 28 phosphorylated protein that were significantly up or down regulated across all experimental groups.

Figure 3.14: Impact of TLR4 signaling on protein phosphorylation in severe experimental asthma. Unsupervised hierarchical clustering on all phosphorylated proteins identified in PBS and HDM challenged WT and TLR4-/- mice was performed using Perseus 6.3. A multiple sample test (ANOVA) was performed using the log2 intensity values of significantly regulated phosphoproteins. The heat map depicts the intensity of 139 phosphorylated protein that were significantly up or down regulated across all experimental groups.

126

inflammation and AHR in a mouse model of severe asthma. TLR4 or RAGE gene

deletion is sufficient to protect against all major features of asthma in

corticosteroid-sensitive models of the disease (2-7). Thus, our findings indicate

that co-operative signaling down-stream of these receptors is an important

determinant of severe asthma. Moreover, by performing a global

phosphoproteomic analysis of lung tissue samples we have identified the

possible signaling mechanisms involved. Our findings provide unique insights

into molecular mechanisms of severe asthma and expose new targets for

therapeutic intervention, some of which are discussed below.

The C-C motif chemokine CCL3 signals via CCR1 expressed on neutrophils to

regulate key steps involved in their recruitment to sites of inflammation (16). We

demonstrated that inhibition of airway neutrophilia in RAGE/TLR4 gene-deficient

mice was associated with inhibition of CCL3 protein levels in BALF. In addition,

we found that CCR1 phosphorylation is up-regulated upon induction of severe

asthma in wild-type but not TLR4/RAGE gene-deficient mice (Table 3.1, Fig

3.12). These data, together with KEGG pathway analysis which revealed

significant enrichment of the chemokine signaling pathway in severe

experimental asthma suggest that activation of CCL3-CCR1 signaling down-

stream of RAGE/TLR4 ligation is an important driver of corticosteroid-resistant

neutrophilic inflammation in severe asthma.

During chemotaxis, neutrophil migration is regulated by Rac, a member of the

small guanosine triphosphatases (GTPases) that cycle between inactive

guanosine diphosphate (GDP)–bound and active guanosine triphosphate (GTP)–

127

bound states. Rac is activated by guanine-nucleotide exchange factors (GEFs)

which remove GDP, thus allowing excess free GTP to bind to Rac. The GEFs

contain a variety of localization motifs such as pleckstrin homology (PH) domains

and the DOCK homology region (DHR)–1, both of which bind to

phosphatidylinositol 3,4,5-trisphosphate (PIP3), a lipid product of

phosphoinositide 3-kinases (PI3Ks) (17). Of note, the Rac GEF DOCK2 has been

identified as an important regulator of neutrophil chemotaxis (18-20). Moreover,

we observed increased DOCK2 phosphorylation upon induction of severe

asthma in wild-type but not TLR4/RAGE gene-deficient mice (Table 2.1, Fig

3.12), suggesting that DOCK2 may regulate the neutrophilic response down-

stream of CCL3-CCR1 signalling.

Indeed, while no studies have specifically examined DOCK2 activation down-

stream of CCR1-CCL3 signalling, previous studies have shown that DOCK2

recruitment to the plasma membrane is mediated by PI3Kγ (19), the same PI3K

isoform that mediates CCL3-dependent inflammatory responses (16). Thus,

together, our findings expose a previously unrecognised role for CCL3-CCR1-

DOCK2 signalling in corticosteroid-resistant neutrophilia. Significantly, increased

CCL3 gene expression is observed in bronchoalveolar lavage cells and

peripheral blood cells isolated from adults and children with corticosteroid-

resistant asthma, respectively, providing further support for this notion (21, 22).

Moreover, it has been shown that CCR1 and PI3Kγ deficiency protects against

features of the asthmatic response in experimental mouse models, indicating this

pathway may be amenable to therapeutic targeting (23-25).

128

Severe asthma in children is significantly associated with gene polymorphisms in

the protein programmed cell death 4 (PDCD4) (26), a multifunctional protein that

was recently identified as a critical effector of TLR4 signaling (27). Consistent

with this, our studies indicate that TLR4/RAGE ligation leads to down-stream

phosphorylation and activation of PDDC4 (Table 3.1, Fig 3.12) and in addition,

provide the first experimental evidence for a role for this protein in severe asthma.

Notably, while PDCD4 is required for activation of TLR4-dependent inflammatory

responses, it also functions as a negative regulator of TLR4 signaling.

Mechanistically this occurs as a result of miR-21 induction upon TLR4 ligation as

miR-21 decreases PDCD4 protein abundance which ultimately leads to a

decrease in TLR4 signaling (27). Previous studies by Hansbro’s laboratory

demonstrated increased expression of miR-21 in the lung in an experimental

mouse model of severe corticosteroid-resistant asthma (28). Interestingly,

although specific inhibition of miR-21 in this model protected against AHR, it had

no significant effect on corticosteroid-resistant airway inflammation. Our studies

indicate that PDCD4 is potentially a better target than miR-21 as it is down-stream

of mi-R21 and its inhibition is associated with significant protection against both

AHR and neutrophilic inflammation in severe asthma.

Innate lymphoid cells (ILCs) are enriched at mucosal surfaces where they play a

critical role in immune surveillance. Studies in mice have shown that RAGE is

required for lung-specific accumulation of group 2 innate lymphoid cells (ILC2s)

in experimental models of allergic asthma (7). Extending this finding, we have

shown that RAGE/TLR4 signaling activates NFIL3 (also known as E4BP4) (Fig

3.12), a basic leucine zipper transcription factor required for the development of

129

all ILCs (29, 30). ILCs consist of three distinct subsets: group 1 ILCs (ILC1) which

produce IFN-γ, group 2 ILCs (ILC2) which produce type 2 cytokines such as IL-5

and IL-13 and group 3 ILCs (ILC3) which produce type 17 cytokines such as IL-

17 and IL-22. Significantly, ILC2s isolated from the bronchoalveolar lavage fluid

of asthmatic subjects are resistant to the anti-inflammatory actions of

corticosteroids, indicating these cells potentially contribute to corticosteroid

resistant inflammation in severe asthma (31). This notion is further supported by

data from the U-BIOPRED severe asthma cohort which identified 3

transcriptomic-associated clusters (TACs) based on hierarchical clustering of

sputum gene expression data. Of note, subjects in TAC1 were characterized by

eosinophilic inflammation and ILC2 activation while subjects in TAC2 were

characterized by neutrophilic inflammation, ILC1 and ILC3 activation (32).

Consistent with these observations, we have shown that inhibition of NFIL3

phosphorylation in RAGE/TLR4 gene-deficient mice is associated with protection

against severe corticosteroid-resistant asthma; these findings provide the first

evidence of a functional link between all three ILC subsets and airway

inflammatory and functional abnormalities in severe asthma.

130

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Chapter 4

MACROPHAGE MIGRATION INHIBITORY FACTOR

PROMOTES GLUCOCORTICOID RESISTANCE IN

SEVERE ASTHMA

136

INTRODUCTION

Asthma incorporates a spectrum of respiratory conditions characterized by

chronic airway inflammation, airway remodeling and variable airflow limitation.

This spectrum includes a group of patients with severe disease, in whom

symptom control is not achieved or maintained despite treatment with

glucocorticoids. Severe asthma is a heterogeneous clinical condition

underpinned by diverse cellular and molecular mechanisms. The airway

inflammatory response may be driven predominantly by either eosinophils or

neutrophils; in some patients, both eosinophils and neutrophils are involved,

while in others, there is no evidence of either eosinophilic or neutrophilic

inflammation. Hence, the pattern of granulocytic airway inflammation reflects an

important aspect of the underlying biological heterogeneity (1).

The NLRP3 inflammasome is an intracellular molecular complex that regulates

the processing and secretion of IL-1 family cytokines implicated in the neutrophilic

asthmatic response (2). Notably, the NLRP3 inflammasome was among the top

20 differentially expressed genes in sputum cells from patients with severe

asthma, relative to those with mild-moderate asthma or healthy control subjects,

in the U-BIOPRED cohort (3). Moreover, significant correlation between NLRP3,

neutrophilic inflammation and asthma severity has also been demonstrated, and

inhibition of NLRP3 protects against glucocorticoid-resistant neutrophilic

inflammation in mouse models of severe asthma (3, 4).

MIF is an immunomodulatory molecule implicated in many chronic inflammatory

conditions, including asthma (5, 6). We recently identified a highly specific role

137

for MIF in the formation of the NLRP3 inflammasome and have shown that it

facilitates NLRP3-dependent IL-1β release in macrophages (7). Moreover, MIF

counter-regulates the anti-inflammatory actions of glucocorticoids (8-11),

promotes neutrophil recruitment to the lung (12-15), and upregulates expression

of TLR4, a pattern-recognition receptor associated with airway neutrophilia in

asthma (16, 17). Together this suggests that MIF could be a critical driver of

glucocorticoid-resistant neutrophilic inflammation in severe asthma.

Importantly, increased levels of MIF have been detected in the airways and serum

of asthmatic patients (5, 6), while studies in animal models of ovalbumin (OVA)-

induced asthma have established a role for MIF in the eosinophilic asthmatic

response and other features of asthma including airway wall remodeling and

airway hyperreactivity (18-24). However, to date no studies have examined

whether MIF is an important determinant of airway neutrophilia and glucocorticoid

insensitivity typical of severe asthma. In this study, we examined the relationship

between MIF, airway neutrophilia, inflammasome activation and glucocorticoid

signaling in the U-BIOPRED asthma cohort and in a mouse model of severe

asthma.


U-BIOPRED data

The U-BIOPRED project was established to identify multi-dimensional

phenotypes of asthma and new treatment targets using a combination of omics

technologies and systems biology approaches (25). Based on hierarchical

clustering of differentially-expressed genes between eosinophilic and non-

138

eosinophilic subjects, three transcriptomic-associated clusters (TACs) were

described (26). S100A9 and MIF protein expression in sputum samples was

measured used the SOMAscan proteomic assay (SomaLogic Inc., Boulder, CO).

Analysis of S100A8, S100A9, NLRP3, TLR4, DUSP1, TSC22D3 (GILZ) and

ANXA1 genes in sputum samples was performed using Array Studio software

(Accession number: GSE76262, Omicsoft Corporation, Research Triangle Park,

NC, USA). Detailed methodology for protein and gene expression analysis has

been described previously (26).

Mouse model of severe asthma

Female C57BL/6 mice were purchased from the Australian Resource Centre

(Perth, Australia) and housed under specific pathogen free conditions. All

procedures were performed at the University of Technology Sydney (UTS) under


Scientific Purposes, and approved by the UTS Animal Care and Ethics

Committee. At 8 weeks of age, mice were sensitized to HDM allergen (100μg)

(Dermatophagoides pteronyssinus, Greer Laboratories, Lenoir, NC, USA)

emulsified with an equal volume of complete Freund’s adjuvant (CFA) (Sigma-

Aldrich, St Louis, MO, USA) via subcutaneous injection. On day 14, mice were

challenged with HDM (100μg) via the intranasal route. Control mice were

sensitized and challenged with PBS only. ISO-1 (4,5-Dihydro-3-(4-

hydroxyphenyl)-5-isoxazoleacetic acid methyl ester, 35mg/Kg, Tocris

Bioscience) or its vehicle (5% DMSO in PBS) were administered 30 min before

HDM challenge or 30 min before and 6 h post HDM challenge via intraperitoneal

injection. Dexamethasone (9α-Fluoro-16α-methyl-11β,17α,21-trihydroxy-1,4-

139

pregnadiene-3,20-dione, 1mg/Kg, Sigma Aldrich) was administered 30 min prior

to HDM challenge via oral gavage (see study design, Suppl Fig 1A).

Measurement of airway hyperreactivity and airway inflammation was performed

as described below. Data are represented as the mean ± SEM and were

analyzed using ANOVA followed by Bonferroni post-test for multiple comparisons

or Student’s two-tailed t-test, as indicated. A P value less than 0.05 was

considered statistically significant.

Measurement of airway hyperreactivity

Airway hyperreactivity (AHR) was measured 24 h after allergen challenge on day

15 by forced oscillation technique using FlexiVent apparatus (SCIREQ, Montreal,

Canada). Mice were anesthetized using a cocktail of xylazine (0.2mg/10gm) and

ketamine (0.4mg/10gm body weight). An 18-gauge blunt needle was inserted into

the trachea and mice were kept under mechanical ventilation at 200 breaths/min

with a delivered tidal volume of 0.25 mL against a positive end-expiratory

pressure (PEEP) of 3 cm H2O. Total lung resistance (Rrs), compliance (Crs) and

elastance (Ers), proximal airway resistance (Rn) and distal airway dampening (G)

and elastance (H) were determined by administering increasing doses of

nebulized methacholine (0 to 10 mg/mL) (Sigma-Aldrich, St Louis, MO, USA).

Analysis of bronchoalveolar lavage fluid

Once lung function measurements were completed, mice were exsanguinated

after a lethal dose of pentobarbital (100 mg/kg). The lungs were lavaged twice

with 0.5 mL sterile Hanks Balanced Salt Solution (HBSS). The collected fluid was

spun at 3000 rpm for 10 min at 4oC. Cell supernatants were retained for analysis

140

of cytokine/chemokine expression, while cell pellets were resuspended in sterile

HBSS for enumeration of total and differential cell counts. To perform differential

cell counts, cells were spun on glass slides using a Cytospin 4 Cytocentrifuge

(Thermo Fisher Scientific) and stained with Diff-Quik®. A total of 200 cells were

counted. The concentration of MIF and LTB4 in BALF was determined using

commercial ELISA assays (R&D Systems). The concentration of other cytokines

and chemokines in BALF were determined using a customized Magnetic Luminex

assay (R&D systems) using the MAGPIX® System. Five parameter logistic

regression was performed to predict the concentration of unknown samples.

Quantification of airway inflammation and mucus production

After collection of BALF, the left lung was inflated with neutral buffered formalin

(NBF), excised and fixed in NBF. Lung sections were stained with hematoxylin

and eosin (H&E) and airway inflammation (inflammatory cell infiltrate) semi-

quantified by blinded scoring of the inflammatory cell infiltrate surrounding each

airway (27). Scores ranged from 0-4 (0: no inflammatory cell infiltrates around

airway, 1: low level cell infiltrates around part of airway, 2: moderate cell infiltrates

around part of or entire airway, 3: significant inflammatory cell infiltrates around

part of or entire airway, 4: airway completely surrounded by inflammatory cell

infiltrates). Mucus producing cells were identified by Periodic acid-Schiff (PAS)

staining and scored blindly from 0 to 5 based on percentage of PAS positive

airway epithelial cells (AEC) (0: 0% of total AEC, 1: 1-10% of total AEC, 2: 10-

30% of total AEC, 3: 30-50% of total AEC, 4: 50-80% of total AEC, 5: >80% of

total AEC)(27). Five airways were scored per mouse. All sections were imaged

on Aperio Scanscope XT and Leica DM750 Brightfield microscope.

141

Immunoblotting

NLRP3, IL-1β and ANXA1 protein were measured in lung homogenates and/or

BALF by immunoblotting. To prepare lung homogenates, the right lung was lysed

using RIPA buffer containing protease and phosphatase inhibitors (cOmplete™

ULTRA and PhosSTOP™, Roche Diagnostics, Australia). Protein concentrations

were determined using the Pierce™ BCA Protein Assay Kit according to the

manufacturer’s instructions. Proteins were loaded onto 4-12% bis-tris gels and

separated by electrophoresis at 200V for 50 min. 40 µg and 1 µg of total protein

was loaded onto gels to measure NLRP3 and ANXA1 in lung homogenates,

respectively; and 10 µg and 1 µg of total protein was loaded onto gels to measure

IL-1β and ANXA1 in BALF, respectively. Following electrophoresis, proteins were

transferred to a polyvinylidene difluoride (PVDF) membrane using the iBlot 2 Dry

Blotting System (Life Technologies). PVDF membranes were then blocked with

5% non-fat milk powder in Tris-buffered saline containing 0.1% Tween (TBST)

for 1 h at room temperature, prior to overnight incubation with primary antibodies

for NLRP3 (Adipogen Life Science #AG-20B-0014-C100 1:500 dilution), IL-1β

(BioVision INC #5129-100 1:500 dilution) or ANXA1 (R&D Systems #MAB37701

1:20000 dilution) at 40C. To ensure even protein loading, PVDF membranes were

incubated with primary antibody for GAPDH (Santa Cruz Biotechnology #sc-

32233 1:1000 dilution) (lung homogenates) or stained with 0.1% Ponceau S

(Fisher Biotech) in 5% acetic acid (BALF). PVDF membranes were then washed

with TBST three times (5 min each) and incubated with HRP-linked anti-mouse

IgG secondary antibodies (GE Healthcare #NA931-1ML 1:2000 dilution) as

appropriate, for 1 hour at room temperature. PVDF membranes were then

washed with TBST three times (5 min each). Protein bands were visualized using

142

enhanced chemiluminescence (ECL) (Amersham, GE Healthcare) and

densitometric analysis was performed using Image J software (v1.47).

RESULTS

MIF expression is associated with neutrophilic inflammation and

inflammasome activation

Previous data from the U-BIOPRED cohort identified 3 transcriptomic-associated

clusters (TACs) based on hierarchical clustering of sputum gene expression data.

TAC2 was associated with neutrophilia and NLRP3 activation (26). In human

neutrophils, MIF co-localizes with the S100A8/A9 heterodimeric complex which

makes up about 40% of the cytosolic content in these cells (28). Thus, to

determine whether there is an association between neutrophilic inflammation and

MIF expression, we examined sputum protein abundance of MIF and S100A9

measured by SOMAscan® Assay platform across the three TACs identified in U-

BIOPRED (26). Compared to subjects in TAC1 and TAC3, subjects in TAC2 had

significantly elevated levels of MIF and S100A9 protein (Fig 4.1A, B). S100A8

was not available on this platform.

Analysis of gene expression data also revealed significantly elevated levels of

S100A8 and S100A9, but not MIF mRNA in the TAC2 group (Fig 4.1C, D, Fig

4.2). Moreover, consistent with our previous analysis demonstrating a highly

significant positive correlation between NLRP3 and sputum neutrophil counts in

U-BIOPRED subjects (3), NLRP3 (CIAS1) and TLR4 mRNA were significantly

increased in TAC2 (Fig 4.1E, F). These data suggest an association between

MIF protein abundance and the TAC2 phenotype, in which neutrophilic

143

inflammation and innate immune activation associated with S100A8/A9, TLR4

and NLRP3/IL-1β signaling are dominant features.

Figure 4.1: Expression of innate immune mediators in sputum according to transcriptomic-associated cluster (TAC) status. Protein levels of macrophage migration inhibitory factor (MIF) (A) and S100A9 (B) measured by SOMAscan in log2 relative fluorescent units (RFU). Gene expression levels of S100A8 (C) S100A9 (D) NLR Family Pyrin Domain Containing 3 (NLRP3) (E) and Toll-like receptor 4 (TLR4) (F) measured by microarray and presented as log2 signal intensity values. *P < .05, **P < .01, and ***P < .001

A B

C

Log2

Inte

nsity

D

E F

Log2

(RFU

)

MIF S100A9

Log2

Inte

nsity

S100A8 S100A9

NLRP3/CIAS1 TLR4

TAC1 TAC2 TAC3 TAC1 TAC2 TAC3



Log2

Inte

nsity

Log2

(RFU

)Lo

g2 In

tens

ity

******

******

******

******

******

***

**** **

***

144

Figure 4.2 MIF gene expression according to transcriptomic-associated cluster (TAC) status. MIF gene expression measured by microarray and presented as log2 signal intensity values. *P < .05, **P < .01, and ***P < .001 MIF abundance is associated with reduced expression of the

glucocorticoid-inducible anti-inflammatory protein annexin-A1

To determine whether there is a relationship between MIF and the glucocorticoid

response, we examined the expression of glucocorticoid-inducible anti-

inflammatory genes, including Dual Specificity Phosphatase 1 (DUSP1),

Glucocorticoid-Induced Leucine Zipper (GILZ) encoded by the TSC22D3 gene

and annexin A1 (ANXA1) across the three TACs. Relative to other TACs, subjects

in TAC2 expressed higher or comparable levels of DUSP1 and TSC22D3 mRNA,

indicating these pathways are relatively preserved (Fig 4.3A, B). Notably,

however, compared to TAC1 and TAC3, subjects in TAC2 had significantly lower

levels of ANXA1 mRNA and protein (Fig 4.3C, D). This suggests that MIF

antagonizes glucocorticoid-mediated induction of ANXA1, a pro-resolving

mediator that inhibits neutrophil recruitment (29). Compared to TAC1 and TAC3,

expression of the ANXA1 receptor formyl peptide receptor 2 (FPR2) was

significantly elevated in TAC2, indicating that reduced signaling via FPR2 is an

unlikely explanation for the neutrophilic response (Fig 4.3E). ANXA1 can also

mediate its anti-inflammatory effects by inhibiting the activation of cytosolic

*

MIF

TAC1 TAC2 TAC3

Log2

Inte

nsity

145

phospholipase A2 (cPLA2), a rate limiting enzyme in the process of eicosanoid

synthesis. However, expression levels of the eicosanoid and potent neutrophil

chemoattractant LTB4 were similar across all three TACs, arguing against a

specific role for LTB4 in the neutrophilic response in TAC2 (Fig 4.3F).

Figure 4.3: Expression of steroid responsive genes and mediators in sputum according to transcriptomic-associated cluster (TAC) status. Gene expression levels of dual-specificity phosphatase 1 (DUSP1) (A) TSC22 Domain Family Protein 3 (TSC22D3) (B) annexin A1 (ANXA1) (C) and formyl peptide receptor 2 (FPR2) (E) measured by microarray and presented as log2

A B

C D

E F

Log2

(RFU

)

DUSP1

Log2

Inte

nsity

Log2

Inte

nsity

TSC22D3

ANXA1

FPR2

Log2

Inte

nsity


TAC1 TAC2 TAC3


TAC1 TAC2 TAC3

LTB4

ANXA1

Log2

(RFU

)Lo

g2 (p

g/m

l)Lo

g2 In

tens

ity***

***

***

***

******

******

***

146

signal intensity values. Protein levels of annexin A1 (ANXA1) (D) measured by SOMAscan in log2 relative fluorescent units (RFU). The level of LTB4 (E) was determined by ELISA and presented as pg/ml in each patient sample. * = p<0.05. *P < .05, **P < .01, and ***P < .001 MIF inhibition abrogates neutrophilic airway inflammation and increases

glucocorticoid responsiveness in severe experimental asthma

To examine the role of MIF in the airway neutrophilic response, a mouse model

of severe experimental asthma was used (3). C57BL/6 mice were sensitized with

HDM in the presence of complete Freund’s adjuvant, and then 14 days later

challenged with a single dose of HDM. This protocol elicited a dominant

neutrophilic response, as evidenced by a 10-fold greater abundance of

neutrophils than eosinophils in BALF 24 h post allergen exposure. It also led to

increased levels of MIF and S100A8 protein in the BALF and induced significant

tissue inflammation, mucus hypersecretion and airway hyper-reactivity (AHR)

(Fig 4.4 and Fig 4.7).

147

Figure 4.4. Mouse model of severe experimental asthma. C57BL/6 mice were sensitized with HDM in the presence of complete Freund’s adjuvant, and then challenged with a single dose of HDM after 14 days. (A) Study design (B) MIF and S100A8 protein concentration in BALF. (C) Total and differential cell counts in BALF (D) Total lung resistance (Rrs), compliance (Crs) and elastance (Ers), proximal airway resistance (Rn) and distal airway dampening (G) and elastance (H) were measured using forced oscillation technique. Data represent mean ± SEM. *P < .05, **P < .01, and ***P < .001 vs PBS. #P < .05 and ##P < .01 vs mice HDM. N = 7 – 18 mice per group. HDM = house dust mite.

To determine whether MIF promotes the airway neutrophilic response, we treated

mice with ISO-1, a competitive small molecule inhibitor of MIF activity (30).

P B S H D M0

5 0 0 0

1 0 0 0 0

1 5 0 0 0

2 0 0 0 0

2 5 0 0 0

MIF

pg

/mL

*

P B S H D M

0

2 0

4 0

6 0

8 0

1 0 0

To

tal

Ce

lls

x 1

04

/ m

L

* * * *

P B S H D M0

2 0

4 0

6 0

8 0

Ne

utr

op

hils

x 1

04

/mL

****

P B S H D M0

2

4

6

8

1 0

Eo

sin

op

hils

x 1

04

/mL

****

B a s e lin e 0 1 .2 5 2 .5 5 1 00

2

4

6

M C h m g /m L

Rrs

cm

H2

O.s

/mL

**

****

B a s e lin e 0 1 .2 5 2 .5 5 1 00 .0 0

0 .0 1

0 .0 2

0 .0 3

0 .0 4

M C h m g /m L

Crs

cm

H2

O.s

/mL

**

****

B a s e lin e 0 1 .2 5 2 .5 5 1 00

2 0

4 0

6 0

8 0

1 0 0

1 2 0

1 4 0

M C h m g /m LE

rs c

mH

2O

.s/m

L

**

****

B a s e lin e 0 1 .2 5 2 .5 5 1 00 .0

0 .5

1 .0

1 .5

2 .0

M C h m g /m L

Rn

cm

H2

O.s

/mL

*

****

B a s e lin e 0 1 .2 5 2 .5 5 1 00

7

1 4

2 1

2 8

3 5

M C h m g /m L

G c

mH

2O

.s/m

L

**

****

B a s e lin e 0 1 .2 5 2 .5 5 1 00

3 0

6 0

9 0

M C h m g /m L

H c

mH

2O

.s/m

L **

****

P B S

H D M

P B S H D M0

1 0 0 0 0

2 0 0 0 0

3 0 0 0 0

4 0 0 0 0

S1

00

A8

pg

/mL

* * *

148

Previous studies have shown that a single administration of ISO-1 at a dose of

35 mg/kg inhibits airway neutrophilia induced by the administration of

recombinant MIF in naïve mice (13). Thus we trialed two dosing regimens; in the

first, ISO-1 (35 mg/kg) was administered 30 min prior to allergen challenge, whilst

in the second, it was administered 30 min prior and 6 h post allergen challenge.

A single administration of ISO-1 30 min prior to HDM challenge had no significant

effect on eosinophilic or neutrophilic inflammation, histological evidence of airway

inflammation, mucus hyper-secretion or AHR (Fig 4.5 and Fig 4.7). However,

when administered 30 min prior and 6 h post HDM challenge, ISO-1 significantly

inhibited neutrophil numbers in BALF, tissue inflammation and AHR. ISO-1

treatment also reduced eosinophil numbers and mucus secretion, although these

effects were not statistically significant (Fig 4.5 and Fig 4.7).

149

Figure 4.5: ISO-1 inhibits neutrophilic inflammation and AHR in severe experimental asthma. Mice were treated with ISO-1 30 min prior to HDM challenge (ISO-1) or 30 min prior and 6 h post HDM challenge (ISO-1 bid). (A) Total and differential cell counts in BALF (B) Total lung resistance (Rrs), compliance (Crs) and elastance (Ers), proximal airway resistance (Rn) and distal airway dampening (G) and elastance (H) were measured using forced oscillation technique. Data represent mean ± SEM. *P < .05, **P < .01, and ***P < .001 vs PBS. #P < .05 and ##P < .01 vs mice HDM. N = 7 – 18 mice per group. HDM = house dust mite. Because MIF has been reported to counteract the anti-inflammatory effects of

glucocorticoids (9-11, 31), we hypothesized that it contributes to the development

of glucocorticoid-resistant neutrophilic inflammation in severe asthma. To test

this, mice were treated with dexamethasone (Dex, 1 mg/kg) together with a single

dose of ISO-1 (35 mg/kg) 30 min prior to allergen exposure. Treatment with Dex

alone significantly inhibited airway eosinophilia and AHR, and caused a marked,

0

2 0

4 0

6 0

8 0

1 0 0

To

tal

Ce

lls (

x 1

04

/ m

L)

#

** **

**

**

0

20

40

60

80

Neu

troph

ils (x

104 /m

L)

##

**** **

**

0

2

4

6

8

1 0

Eo

sin

op

hils

(x

10

4/m

L) ** **

**

**0 .0 7

B a s e lin e 0 1 .2 5 2 .5 5 1 00

1

2

3

4

5

6

7

M C h m g /m L

Rrs

cm

H2

O.s

/mL

# #

*

**

B a s e l i n e 0 1 . 2 5 2 . 5 5 1 0

0 . 0 0

0 . 7 5

1 . 5 0

2 . 2 5

M C h m g / m L

Rn

cm

H2

O.s

/mL

#

*

* *

B a s e l i n e 0 1 . 2 5 2 . 5 5 1 0

0

1 5

3 0

4 5

M C h m g / m L

G c

mH

2O

.s/m

L

# #

*

* *

B a s e l i n e 0 1 . 2 5 2 . 5 5 1 0

0

2 5

5 0

7 5

1 0 0

M C h m g / m L

H c

mH

2O

.s/m

L

#*

* *

P B S

H D M

H D M + V E H

H D M + IS O -1

H D M + IS O -1 b id

B a s e l i n e 0 1 . 2 5 2 . 5 5 1 0

0 . 0 0

0 . 0 1

0 . 0 2

0 . 0 3

0 . 0 4

M C h m g / m L

Crs

cm

H2

O.s

/mL

*

* *

B a s e l i n e 0 1 . 2 5 2 . 5 5 1 0

0

2 0

4 0

6 0

8 0

1 0 0

1 2 0

1 4 0

1 6 0

M C h m g / m L

Ers

cm

H2

O.s

/mL

*

* *

150

but non-significant reduction in mucus secretion. At this dose, however, Dex had

no significant effect on the airway neutrophilic response or histological evidence

of airway inflammation. However, when mice were treated with the combination

of Dex and ISO-1, a striking reduction in airway neutrophil numbers, inhibition of

tissue inflammation, and further inhibition of AHR was observed (Fig 4.6 and Fig

4.7). Treatment of mice with Dex alone or combined treatment with Dex and ISO-

1 had no effect on the concentration of MIF in BALF, indicating that enhanced

glucocorticoid efficacy was not due to an inhibitory effect of Dex on MIF release

(Table 4.1). Taken together, these data suggest that the activity of MIF constrains

the anti-inflammatory effects of glucocorticoids on neutrophil-dependent severe

experimental asthma.

151

Figure 4.6 ISO-1 restores glucocorticoid responsiveness in severe experimental asthma. Mice were treated with ISO-1, Dex or ISO-1 + Dex 30 min prior to HDM challenge. (A) Total and differential cell counts in BALF (B) Total lung resistance (Rrs), compliance (Crs) and elastance (Ers), proximal airway resistance (Rn) and distal airway dampening (G) and elastance (H) were measured using forced oscillation technique. Data represent mean ± SEM. *P < .05, **P < .01, and ***P < .001 vs PBS. #P < .05 and ##P < .01 vs mice HDM. N = 7 – 18 mice per group. HDM = house dust mite.

B a s e lin e 0 1 .2 5 2 .5 5 1 00

1

2

3

4

5

6

7

M C h m g /m L

Rrs

cm

H2

O.s

/mL

δ##

##

*

**

*

B a s e lin e 0 1 .2 5 2 .5 5 1 00 .0 0

0 .0 1

0 .0 2

0 .0 3

0 .0 4

M C h m g /m L

Crs

cm

H2

O.s

/mL

###

**

*

B a s e lin e 0 1 .2 5 2 .5 5 1 00

2 5

5 0

7 5

1 0 0

1 2 5

1 5 0

M C h m g /m L

Ers

cm

H2

O.s

/mL

# #

##

δ

**

**

B a s e lin e 0 1 .2 5 2 .5 5 1 00 .0 0

0 .7 5

1 .5 0

2 .2 5

M C h m g /m L

Rn

cm

H2

O.s

/mL

# # ##

*

**

B a s e lin e 0 1 .2 5 2 .5 5 1 00

9

1 8

2 7

3 6

4 5

M C h m g /m L

G c

mH

2O

.s/m

L

δ

## ##

*

**

*

B a s e lin e 0 1 .2 5 2 .5 5 1 00

2 0

4 0

6 0

8 0

1 0 0

1 2 0

M C h m g /m L

H c

mH

2O

.s/m

L

# ###*

**

*

0

2 0

4 0

6 0

8 0

1 0 0

To

tal

Ce

lls (

x 1

04

/ m

L)

# #

#

* * * *

* *

* *

*

0

2 0

4 0

6 0

8 0

Ne

utr

op

hil

s (

x 1

04

/mL

)

# #

δ

* ** *

* *

* *

*

0

2

4

6

8

1 0

Eo

sin

op

hil

s (

x 1

04

/mL

)

#

# #

* * * *

* *

* *

*

P B S

H D M

H D M + V E H

H D M + IS O -1

H D M + D E X

H D M + IS O -1 + D E X

152

Figure 4.7: Effects of ISO-1 and/or Dex on tissue inflammation and mucus secretion. Mice were treated with ISO-1 30 min prior and 6 h post HDM challenge (ISO-1 bid); or were treated with ISO-1, Dex or ISO-1 + Dex 30 min prior to HDM challenge. Airway inflammation (A) and mucus production (B) were assessed by hematoxylin and eosin (H&E) and Periodic-Acid Schiff (PAS) staining, respectively. Data represent mean ± SEM. *P < .05 vs PBS. #P < .05 and ##P < .01 vs HDM (house dust mite). N = 5 – 6 mice per group. Representative images for H&E (x10 original magnification) and PAS (x40 magnification) are shown. Scale bars, 60µm.

MIF inhibition synergizes with glucocorticoid-mediated suppression of

inflammatory gene expression in severe experimental asthma

To identify possible mechanisms by which MIF mediates airway neutrophilia and

constrains glucocorticoid efficacy in severe asthma, we measured a broad range

of inflammatory mediators in the lung. Administration of ISO-1 30 min prior to and

A

B

0 .0

0 .4

0 .8

1 .2

Air

wa

y M

ucu

s S

core

*

*

0

1

2

3

Lu

ng

In

flam

ma

tion

Sco

re **

**

#

##

0 .07

P B S

H D M

H D M + V E H


H D M + IS O -1

H D M + D E X

H D M + IS O -1 + D E X

153

6 h post allergen led to a significant reduction in the concentration of S100A8 in

BALF, consistent with the observed reduction in neutrophil numbers. However,

MIF inhibition had no significant effect on NLRP3 protein expression in lung tissue

homogenates nor IL-1β or IL-1α release in BALF (Fig 4.8A, B and Table 4.1). MIF

inhibition also had no effect on the secretion of a number of

cytokines/chemokines that promote neutrophil chemotaxis into the lung, including

CXCL1, TNF-α, IFN-γ, IL-23, IL-17A and IL-17E (we did not detect significant

induction of LTB4 release in this model) (Table 4.1). Apart from CCL11, MIF

inhibition had no significant inhibitory effect on the release of type 2

cytokines/chemokines involved in the eosinophilic response (Table 4.1).

Furthermore, with the exception of S100A8, TNF-α and IL-1α, Dex had no

significant inhibitory effect on the release of any other inflammatory mediator

measured (Fig 4.8A, B, and Table 4.1). Notably, however, following combined

treatment with Dex and ISO-1, we observed significant inhibition of a number of

inflammatory mediators, including NLRP3, IL-1β, IFN-γ, GM-CSF, CCL3, CCL11

and IL-33 (Table 1, Fig 4.8A, B). These data suggest that MIF inhibition

synergizes with glucocorticoid-mediated suppression of inflammatory gene

expression in severe experimental asthma.

154

Figure 4.8. Effects of ISO-1 and/or Dex on NLRP3 expression, IL-1β release. Mice were treated with ISO-1 30 min prior and 6 h post HDM challenge (ISO-1 bid); or were treated with ISO-1, Dex or ISO-1 + Dex 30 min prior to HDM challenge. Densitometric analysis of NLRP3 (A) and IL-1β (B) were measured by immunoblotting in lung tissue lysates or BALF. Data represent mean ± SEM. *P < .05 vs PBS. #P < .05 and ##P < .01 vs HDM (house dust mite). N = 8 mice per group.

0

2 0 0 0

4 0 0 0

6 0 0 0

8 0 0 0

1 0 0 0 0

1 2 0 0 0

IL-1

β A

rbitr

ary

Un

its * *

* * * *

* *

* *

#

0

2

4

6

8

1 0

1 2

NL

RP

3/G

AP

DH

**

#

** **

**

**

IL -1 β 1 7 k D a

P o n c e a u S

N L R P 3

G A P D H

1 1 3 k D a

3 7 k D a

P B S

H D M

H D M + V E H


H D M + IS O -1

H D M + D E X

H D M + IS 0 -1 + D E X

155

Table 4.1: Inflammatory mediators in BALF

Mediator pg/mL

PBS

HDM

HDM + Veh

HDM + ISO-1 bid

HDM + ISO-1

HDM + Dex

HDM + ISO-1 + Dex

MIF 5145.06 ± 886.22

10287.29 ± 1866.01* 11934.87 ± 3184.10 13745.12 +

2196.87 12195.19 ± 1261.15

9218.23 + 2190.76

8894.26 + 1115.88

S100A8 187.79 ± 10.76 25313.20 ± 1612.08*

22413.07 ± 2756.60*

15992.12 ± 2994.56*#

22814.74 ± 2103.93*

15714.75 ± 2331.65*#

12092.80 ± 879.14*#

LTB4 101.73 ± 20.11 81.64 ± 10.49 84.27 ± 16.12 92.61 ± 24.53 112.10 ± 22.98 83.97 ± 15.88 92.16 ± 13.6 IFN-γ 1.20 ± 0.41 452.03 ± 89.49* 318.21 ± 96.10* 257.00 ± 70.55 354.87 ± 64.57* 295.39 ± 58.63* 153.45 ± 57.21# TNF-α 0.26 ± 0.05 33.63 ± 6.44* 27.91 ± 10.32* 19.97 ± 6.42 28.73 ± 5.21 11.66 ± 3.75# 6.20 ± 1.39# GM-CSF 0.87 ± 0.15 6.88 ± 0.95* 5.06 ± 1.32* 4.08 ± 0.64 6.12 ± 0.84* 4.85 ± 1.11* 2.72 ± 0.35# CXCL1 11.77 ± 4.11 43.08 ± 5.08 31.21 ± 5.71 38.97 ± 6.24 43.26 ± 2.63* 30.83 ± 5.87 27.91 ± 6.04 CCL2 0.00 ± 0.00 167.67 ± 14.45* 215.10 ± 50.17* 161.38 ± 46.09* 200.68 ± 18.54* 120.45 ± 36.70* 47.32 ± 14.57* CCL3 0.43 ± 0.08 39.22 ± 3.45* 27.66 ± 5.44* 24.84 ± 6.40* 33.51 ± 3.99* 24.58 ± 6.02* 14.01 ± 1.90# CCL5 25.44 ± 4.29 194.22 ± 26.35* 247.52 ± 92.85* 187.56 ± 51.00* 201.37 ± 28.37* 113.89 ± 19.33* 101.41 ± 23.00 CCL11 13.5 ± 0.9 44.32 ± 5.98* 40.03 ± 6.62* 20.36 ± 5.22# 42.27 ± 5.76* 24.31 ± 6.09* 10.24 ± 2.86# IL-1α 4.81 ± 1.61 27.92 ± 1.46* 27.80 ± 4.75* 21.67 ± 4.33* 30.24 ± 2.29* 15.82 ± 1.72*# 12.63 ± 1.93*# IL-4 1.95 ± 0.80 62.52 ± 7.80 60.02 ± 19.15 66.36 ± 21.51 105.21 ± 17.36 131.90 ± 49.25 115.64 ± 32.40 IL-5 0.47 ± 0.08 13.10 ± 2.86* 10.86 ± 2.14* 10.72 ± 2.17* 7.66 ± 0.95 16.27 ± 2.80* 6.63 ± 0.65 IL-6 2.42 ± 0.52 131.08 ± 27.13* 102.46 ± 24.32* 122.45 ± 21.80* 164.01 ± 22.42* 124.85 ± 28.92* 130.48 ± 27.41* IL-10 0.52 ± 0.23 2.75 ± 0.12* 3.24 ± 0.61* 1.95 ± 0.46 2.78 ± 0.20* 1.96 ± 0.36* 1.06 ± 0.31 IL-13 6.81 ± 0.77 20.22 ± 2.33* 25.70 ± 6.40* 16.88 ± 2.30* 22.02 ± 1.59* 18.64 ± 3.58* 14.60 ± 3.67* IL-17A 0.84 ± 0.35 8.84 ± 1.03* 10.91 ± 2.90* 7.77 ± 1.67 10.965 ± 2.24* 8.55 ± 1.93* 4.15 ± 1.40 IL-17E 1.81 ± 1.20 38.72 ± 3.91* 43.71 ± 13.07* 24.09 ± 7.92 43.94 ± 7.46* 33.78 ± 9.56* 12.19 ± 5.30* IL-23 p19 30.37 ± 6.62 105.15 ± 10.28* 125.87 ± 41.53* 82.95 ± 15.57 114.97 ± 9.01* 65.33 ± 8.16 56.15 ± 9.96 IL-33 5.89 ± 2.02 23.45 ± 3.25* 26.97 ± 7.63* 15.44 ± 4.20 26.47 ± 3.31* 13.38 ± 3.92 6.13 ± 3.08#

156

MIF promotion of proteolytic cleavage of ANXA1

Given that subjects in TAC2 expressed lower levels of ANXA1 protein, we

examined whether MIF promotes glucocorticoid-resistant neutrophilic

inflammation by inhibiting the expression and/or activity of ANXA1 (10). We

detected robust levels of full-length 37 kDa ANXA1 protein in lung tissue lysates

under basal conditions, and there was no change in abundance under all

experimental conditions examined (Fig 4.9A). In contrast, however, in the BALF

of allergen-challenged mice, but not PBS-treated mice, we detected variable

expression of two protein bands at 33 kDa and 28 kDa, indicating cleavage of

ANXA1 (Fig 4.9A, B). To determine the overall extent of ANXA1 cleavage, we

performed densitometric analysis on each of these protein bands separately and

added the values (Fig 4.9B). This analysis revealed significant cleavage of

ANXA1 in severe experimental asthma. Strikingly, administration of ISO-1 30 min

prior and 6 h post allergen was associated with a significant reduction in the

extent of ANXA1 cleavage (Fig 4.9B). Moreover, whereas administration of either

ISO-1 or Dex alone 30 min prior to allergen challenge had no significant effect on

the extent of ANXA1 cleavage, combined administration of ISO-1 and Dex was

associated with almost complete inhibition of ANXA1 cleavage (Fig 4.9B).

Together, these data suggest that MIF promotes glucocorticoid-resistant

neutrophilic inflammation by enhancing proteolytic cleavage of ANXA1.

157

Figure 4.9. Effects of ISO-1 and/or Dex on annexin A1 cleavage. Mice were treated with ISO-1 30 min prior and 6 h post HDM challenge (ISO-1 bid); or were treated with ISO-1, Dex or ISO-1 + Dex 30 min prior to HDM challenge. (A) Annexin A1 (ANXA1) protein expression was measured by immunoblotting in lung tissue lysate (lanes 1 to 7) and BALF (lanes 8 and 9). Lanes 1 and 8 represent mice treated with PBS; lanes 2 and 9 represent mice treated with HDM. Lanes 3 and 4 represent mice treated with vehicle or ISO-1 30 min prior and 6 h post HDM challenge, respectively; lanes 5, 6, and 7 represent mice treated with ISO-1, Dex, or ISO-1 + Dex 30 min prior to HDM challenge, respectively. Image representative of data from 4 mice (B) Densitometric analysis of ANXA1 measured by immunoblotting in lung tissue lysates or BALF. Data represent mean ± SEM. *P < .05 vs PBS. #P < .05 and ##P < .01 vs HDM (house dust mite). N = 8 mice per group.

DISCUSSION

We have shown that MIF promotes glucocorticoid-resistant neutrophilic

inflammation in severe experimental asthma and have identified a unique

mechanism that underlies this effect. Our studies indicate that MIF inhibition

prevents the cleavage of ANXA1, a glucocorticoid-inducible pro-resolving

P B S

H D M

H D M + V E H


H D M + IS O -1

H D M + D E X

H D M + IS 0 -1 + D E X

0

5 0 0 0

1 0 0 0 0

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158

mediator that inhibits neutrophil recruitment to sites of inflammation. Consistent

with this, subjects with neutrophilic asthma had increased levels of MIF and

decreased levels of ANXA1 in their airways, while MIF inhibition rendered

important glucocorticoid-insensitive features of severe asthma glucocorticoid-

sensitive in a murine model. Our findings suggest that inhibition of MIF may be of

therapeutic benefit in severe asthma.

Notably, we observed reduced levels of both ANXA1 mRNA and protein in TAC2

subjects, which indicates an overall reduction in ANXA1 protein translation in

neutrophil-dominant asthma. A complicating issue in the interpretation of the

clinical data is that it is unclear whether the SOMAscan® Assay platform used to

measure sputum levels of ANXA1 detects full-length ANXA1 and/or its proteolytic

fragments. Moreover, in contrast to our findings here, a recent analysis of the

Severe Asthma Research Program-3 (SARP-3) cohort found no difference in the

levels of ANXA1 protein in the BALF of patients with severe asthma, compared

to those with non-severe asthma and healthy control subjects (32). Again, it is

unclear which protein species is detected by the ELISA assay used to measure

ANXA1 in this study. It is also difficult to make direct comparisons with our

findings given the difference in biological samples tested and assay methods

used. Indeed, while our studies in mice suggest that ANXA1 cleavage is an

important accompaniment to the effects of MIF on the airway neutrophilic

response, further investigations are required to establish whether excessive

ANXA1 cleavage is responsible for the effects of MIF, whether severe

neutrophilic asthma is associated with a reduction in ANXA1 gene expression

159

and/or protein translation, and whether excessive ANXA1 cleavage is a feature

of the human disease.

Our findings are in line with a previous study demonstrating proteolytic cleavage

of native 37 kDa ANXA1 and generation of a ~33 kDa degradation product in a

mouse model of ovalbumin-induced asthma (33). Importantly, however, in

addition to the classical ~33 kDa cleavage product, we detected a smaller

cleavage product at ~28 kDa. An ANXA1 species of ~28 kDa has previously been

detected in activated neutrophils, and is generated following elastase-mediated

proteolysis of the native protein in vitro (34, 35). Cleavage-resistant forms of

ANXA1 exhibit superior anti-inflammatory activity when compared to the native

protein, thus proteolytic cleavage of ANXA1 as seen here in the absence of MIF

inhibition represents a catabolic event that acts to terminate its anti-inflammatory

actions (36) and leads to the generation of pro-inflammatory protein fragments

(37, 38). Williams and colleagues demonstrated that calpain 1-mediated

cleavage of the ANXA-1 N-terminus leads to the production of a ~33 kDa

cleavage product which induces neutrophil transmigration by increasing ICAM-1

clustering around adherent neutrophils and anchoring them to the endothelium

(37). While our findings indicate that extensive proteolysis of ANXA1 accomanies

the airway neutrophilic response in severe asthma, further studies are required

to establish whether proteolytic fragments of ANXA1 actively drive this process.

Previous studies have shown that intratracheal instillation of recombinant MIF in

mice elicits neutrophil recruitment to the alveolar space by inducing alveolar

macrophages to secrete neutrophil chemotactic factors such as CXCL1 and

160

CXCL2 (13). In contrast, the inhibitory effect of ISO-1 we observed on airway

neutrophilia in severe experimental asthma was not associated with a significant

inhibitory effect on CXCL1, IL-1β and other major cytokines/chemokines

implicated in the airway neutrophilic response. We have recently shown that MIF

regulates the activation/assembly of the NLRP3 inflammasome and mediates the

release of IL-1α, IL-1β and IL-18 secretion by macrophages (7). Our finding that

treatment with ISO-1 alone had no effect on IL-1 cytokine production was

therefore unexpected. The striking reduction in airway neutrophilia with MIF

inhibition, in the absence of an effect on cytokine/chemokine secretion, suggests

that MIF-dependent cleavage of ANXA1 may be a major determinant of the

effects of MIF on airway neutrophilic response. However, we did observe

reductions in NRLP3 and IL-1β when MIF inhibition was added to glucocorticoid

treatment, consistent with MIF’s involvement under these conditions.

Although MIF inhibition had no effect on the secretion of pro-neutrophilic

mediators, it significantly inhibited BALF levels of the neutrophil-derived protein

S100A8. This finding, together with evidence of increased MIF, S100A8/A9 and

TLR4 expression in TAC2 subjects with predominant airway neutrophilia further

suggests that MIF activates neutrophil-intrinsic mechanisms that drive their

recruitment to the lung. Pruenster and colleagues showed that neutrophil rolling

on the endothelial surface triggers secretion of the S100A8/A9 complex which

subsequently engages TLR4 in an autocrine manner to induce high affinity

activation of β2 integrins and neutrophil adhesion to the endothelium (39).

Moreover, it has been shown that aged neutrophils (i.e. those that have spent

some time in the circulation) undergo phenotypic changes that allow them to

161

rapidly traffic to sites of inflammation in a TLR4-dependent manner (40). Sub-

cellular localization studies in human neutrophils have demonstrated strong co-

localization between MIF and S100A8 in cytosolic pools (28). Thus, given that

MIF also regulates expression of TLR4 in innate immune cells (17), we speculate

that molecular cross-talk between MIF, S100A8/A9, TLR4 and ANXA1 underpins

the development of glucocorticoid-resistant airway neutrophilia in severe asthma.

MIF acts directly on eosinophils to promote their differentiation, activation,

migration and survival and is well recognized as a mediator of eosinophilic

inflammation in asthma and other eosinophilic-mediated conditions (5, 6, 18-24,

41-43). Consistent with this, MIF inhibition was associated with significant

inhibition of the eosinophil-active chemokine CCL11 and a marked reduction in

eosinophil numbers in BALF. Of note, Vieira-de-Abreu and colleagues have

shown that MIF induces eosinophils to secrete pre-formed CCL11, and that

CCL11 acts in an autocrine/paracrine manner to induce release of pre-formed

MIF. Importantly, however, while this positive feedback loop was required for

eosinophil activation, it was not required for eosinophil recruitment to the site of

inflammation (24). This latter observation, together with the fact that MIF inhibition

had little impact on the local secretion of cytokines/chemokines in the lung

suggests that the inhibitory effect of ISO-1 on CCL11 was most probably a result

of reduced neutrophil trafficking. It has been shown that activated neutrophils

induce eosinophil trans-basement membrane migration in a TLR4-dependent

manner (44). Moreover, Waddell and colleagues demonstrated a strong positive

correlation between expression of S100A8/A9, CCL11 and eosinophil numbers

at the site of intestinal inflammation in experimental colitis and further showed

162

that S100A8/A9 induces CCL11 release in macrophages (45). Thus, it is possible

that reduced neutrophil trafficking to the lung and the associated reduction in

S100A8/A9 led to a reduction in CCL11 production by lung macrophages, and

subsequent reduction in eosinophil recruitment. Although subjects in TAC2 are

characterised by neutrophilic inflammation, about one third also have increased

numbers of airway eosinophils (26). Thus, MIF represents a potential therapeutic

target for subjects with neutrophilic asthma, including those with secondary

eosinophilic involvement.

We have previously shown that MIF over-rides the anti-inflammatory activity of

glucocorticoids by inhibiting glucocorticoid-mediated expression of the anti-

inflammatory protein GILZ, which then leads to down-stream inhibition of DUSP-

1, a critical inhibitor of MAP Kinase signaling (11). We have also previously

demonstrated that ANXA1 is required for dexamethasone-mediated up-

regulation of GILZ and DUSP-1 in a cell-type specific manner (46, 47). Moreover,

others have shown that MIF inhibits basal and glucocorticoid-mediated

expression of ANXA1 in RAW 264.7 macrophages (10). Given these

observations, and our findings here, it is possible that MIF over-rides the anti-

inflammatory effects of glucocorticoids via a common pathway that involves

ANXA1. Although reduced ANXA1 gene and protein expression was not

associated with a concomitant reduction in GILZ and DUSP-1 mRNA in TAC2

subjects, this does not exclude altered function at the protein level. Indeed, we

have previously demonstrated reduced DUSP-1 expression, and a concomitant

increase in p38 MAPK activation in macrophages from patients with severe

asthma, compared to those with non-severe asthma (48). Moreover, we have

163

shown that p38 MAPK inhibition enhances glucocorticoid-mediated suppression

of monocyte and macrophage cytokine release in severe asthma (49, 50). MIF

promotes neutrophil trafficking to sites of inflammation via p38 MAPK dependent

pathways (51). This together with the fact that ANXA1 negatively regulates p38

MAPK activity (46), suggests that MIF inhibition might restore corticosteroid

sensitivity in severe asthma via down-stream effects on p38 MAPK activity.

In summary, our findings indicate that MIF is an important mediator of severe

asthma, constrains the efficacy of glucocorticoids, and facilitates cleavage of

ANXA1. Further investigation of the mechanisms by which MIF inhibition protects

against airway neutrophilia and restores glucocorticoid sensitivity in severe

asthma is warranted, and may unveil novel therapeutic strategies.

164

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173

Chapter 5

THE PARASITIC 68-MER PEPTIDE FHHDM-1 INHIBITS

MIXED GRANULOCYTIC INFLAMMATION AND AIRWAY

HYPERREACTIVITY IN EXPERIMENTAL ASTHMA

Tanaka Aa*, Allam VSRRb*, Simpson Jc, Tiberti Na, Shiels Jd,e, To Ja, Lund Ma,

Combes Va, Weldon Sa, Taggart Ce, Dalton JPd, Phipps Sc, Sukkar MBb*,

Donnelly Sa*.

The Journal of allergy and clinical immunology (2018)141: 2316-2319.

Author affiliations

aSchool of Life Sciences, Faculty of Science, The University of Technology

Sydney, Ultimo, NSW, Australia

bDiscipline of Pharmacy, Graduate School of Health, The University of

Technology Sydney, Ultimo, NSW, Australia cQIMR Berghofer Medical Research Institute, Herston, QLD, Australia dSchool of Biological Sciences, Queen’s University, Belfast, Northern Ireland eAirway Innate Immunity Group (AiiR), Centre for Experimental Medicine (CEM),

School of Medicine, Dentistry and Biomedical Sciences, Queen’s University

Belfast, Northern Ireland

* These authors contributed equally

174

Clinical Implications: Peptides secreted by parasitic worms (helminths) have potential in the treatment

of asthma and other respiratory conditions in which eosinophilic and/or

neutrophilic inflammation plays a pathological role.

Capsule Summary A peptide derived from the parasitic worm Fasciola hepatica inhibits eosinophilic

and neutrophilic airway inflammation, mucus production and airway

hyperreactivity in a murine model of house dust mite induced asthma.

Key Words: Helminth, Macrophage, House Dust Mite, Lipopolysaccharide, HMGB1, IL-17,

Neutrophils, Eosinophils

Abbreviations: BALF Bronchoalveolar lavage fluid

BMDM Bone marrow derived macrophage

FhHDM-1 Fasciola hepatica helminth defense molecule

LPS Lipopolysaccharide

IPA Ingenuity Pathway Analysis

175

INTRODUCTION

During infection of their mammalian hosts, parasitic worms (helminths) secrete

molecules which modulate the host immune response towards a regulatory

phenotype. This ensures the long-term survival of the parasite within its host and

also prevents excessive tissue damage mediated by inflammatory immune

responses. We reported the identification of a novel immunomodulatory 68-mer

peptide secreted by the animal and human parasite Fasciola hepatica, termed F.

hepatica helminth defense molecule 1 (FhHDM-1)(1). More recently, we showed

that FhHDM-1 ameliorates disease in pre-clinical murine models of type 1

diabetes and multiple sclerosis and therefore represents a new bio-active peptide

with potential as a novel anti-inflammatory pharmacological therapeutic(2).

RESULTS

The mechanism by which FhHDM-1 protects against immune-related

inflammatory disorders is yet to be fully elucidated. In studies thus far, we have

shown that FhHDM-1 preferentially binds to macrophages over neutrophils and

lymphocytes when administered into the peritoneal cavity of immune competent

mice(2). Additionally, the peptide inhibits pro-inflammatory cytokine release in

murine and human macrophages in vitro(2, 3). To pin-point the molecular

pathways by which FhHDM-1 exerts its anti-inflammatory effects, we examined

global transcriptional changes in murine (Balb/c) bone marrow derived

macrophages (BMDMs) treated with a synthetic form of FhHDM-1 for 1 h prior to

stimulation with bacterial LPS for either 6 or 24 h. Gene expression was profiled

on Agilent microarrays containing probes for 41,346 mouse coding transcripts.

This analysis revealed that FhHDM-1 treatment enhanced the expression of

176

1,363 LPS-regulated genes, and decreased the expression of 1,491 genes by ≥

2 fold at 6 h. At 24 h, the expression of 988 LPS-regulated genes was increased

and 1,292 genes was decreased by ≥ 2 fold (Fig 1A; Appendix). Differentially (-

2>fold-change>2, P <0.05 with 5% false discovery rate) expressed genes were

analysed using Ingenuity Pathway Analysis (IPA) to identify signalling pathways

putatively regulated by FhHDM-1 (Fig 1B). Within the top 20 significantly altered

pathways, 16 associated with the activation of pro-inflammatory responses were

repressed by FhHDM-1, consistent with its potent anti-inflammatory activity.

Notably, IPA analysis predicted that FhHDM-1 inhibits high-mobility group box-1

(HMGB1) signalling and IL-17 mediated allergic inflammation (Fig 1B). The anti-

inflammatory effect of the peptide was not specific to Balb/c mice, as BMDMs

derived from C57BL6 mice treated with FhHDM-1 showed the same pattern of

cytokine suppression in response to LPS (Appendix).

No table of figures entries found.Figure 5.1: FhHDM-1 modulates macrophage gene expression FhHDM-1 modulates macrophage gene expression. (A) Clustered profiles for all genes expressed in macrophages that were untreated, treated with LPS

-3.38 0.00 +3.38

Untreated LPS LPS + FhHDM-1

6 hUntreated LPS LPS + FhHDM-1

24 h-4.379 5.126

LPS

LPS

+ Fh

HDM

-1

A B

177

(10ng/ml) or treated with LPS (10ng/ml) and FhHDM-1 (15μM). Changes in fold expression are depicted for 2 experimental replicates. The color-code key indicates fold increases (red) or decreases (blue) in gene expression. (B) Putative canonical pathways significantly altered by FhHDM-1 in macrophages treated with LPS for 6 h, as determined by IPA® analysis. The color-code key indicates the extent of activation (orange) or inhibition (blue) of a pathway.

We have previously shown that HMGB1 is an upstream mediator of the allergic

asthmatic response in mice(4), and that neutralisation of this protein protects

against allergen-induced eosinophilic and neutrophilic inflammation in

experimental asthma(4). IL-17 mediates neutrophilic recruitment to sites of

inflammation and is implicated in the neutrophilic asthma phenotype which is

relatively resistant to treatment with corticosteroids(5). Accordingly, we

hypothesised that FhHDM-1 has therapeutic potential in allergic asthma, and that

it would protect against both eosinophilic and neutrophilic responses

To test our hypothesis, we employed an experimental mouse model of house-

dust mite (HDM) induced allergic asthma, as this model elicits a mixed

granulocytic inflammatory response(4). C57BL6 mice were sensitized to house

dust mite extracts (100µg) or saline intranasally, and after 2 weeks, were

challenged daily with house dust mite extracts (5 µg) or saline, respectively, for

4 days (See study design, Fig 5.2A). Mice received an intravenous injection of

FhHDM-1 (5, 10 or 25 µg dose) 30 min prior to each house dust mite exposure

during the challenge period only. For comparison, mice were also treated with a

homologous helminth defense molecule derived from Schistosoma mansoni

(SmHDM-2) or vehicle control (PBS). FhHDM-1, at both the 10 and 25 µg dose

significantly attenuated allergen induced eosinophil, neutrophil and lymphocyte

178

numbers in the BALF (Fig 5.2B). This effect was specific to FhHDM-1, as neither

SmHDM-2 nor PBS had any effect on airway inflammation.

Figure 5.2: FhHDM-1 protects against allergic airway inflammation FhHDM-1 protects against allergic asthma. (A) Study design. (B) Total and differential cell counts in BALF. Data represent mean ± SEM. *P < .05, **P < .01, and ***P < .001 vs mice treated with PBS. #P < .05 and ##P < .01 vs mice treated with house dust mite. N = 6 – 8 mice per group.

Consistent with this anti-inflammatory effect, FhHDM-1 at both the 10 and 25 µg

dose significantly attenuated allergen-induced airway hyper-reactivity (Fig 5.3C).

FhHDM-1 also significantly reduced histological evidence of tissue inflammation

and mucus production (Fig 5.4D). Moreover, and consistent with data from the

microarray analysis (Appendix) and predictions from the IPA analysis (Fig E1B),

treatment with FhHDM-1 significantly inhibited allergen-induced expression of

macrophage-derived pro-inflammatory mediators, including IL-6, TNF and CCL2,

05

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H D M + F h H D M -1 (1 0 µ g )

H D M + F h H D M -1 (2 5 µ g )

PBS/HDM (5µg)Challenge

Day 0 14 15 16 17 18

PBS/HDM (100µg)Sensitization

Analysis

PBS, SmHDM-2 and FhHDM-1 (i.v)

179

as well as cytokines/chemokines that mediate eosinophil (IL-5, GM-CSF) and

neutrophil (CXCL1, GM-CSF) recruitment (Table 5.2). Furthermore, although not

statistically significant, FhHDM-1 reduced the expression of IL-4 and IL-17A

(Table 5.2).

Figure 5.3: FhHDM-1 inhibits allergen-induced airway hyperreactivity. Total lung resistance and tissue resistance were measured by forced oscillation technique using FlexiVent apparatus. Data represent mean ± SEM. *P < .05, and ***P < .001 vs mice treated with PBS. ##P < .01 vs mice treated with HDM. N = 6 – 8 mice per group.

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180

Figure 5.4: FhHDM-1 inhibits allergen-induced tissue inflammation and mucus production. Lung inflammation score and airway mucus score as assessed by hematoxylin and eosin (H&E) and Periodic-Acid Schiff (PAS) staining, respectively. Representative images of H&E (upper panel, x10 original magnification) and PAS (lower panel, x40 original magnification) are shown. Scale bars, 60µm. Data represent mean ± SEM. ***P < .001 vs mice treated with PBS. ###P < .001 vs mice treated with house dust mite. N = 6 – 8 mice per group.

Table 5.1: Chemokine and cytokine expression in BALF Cytokine/

Chemokine Vehicle (PBS) House dust mite

House dust mite

+ FhHDM-1 P

IL-25/IL-17E ND ND ND

IL-23 ND ND ND

IL-33 ND ND ND

IFN-γ ND ND ND

IL-1β ND ND ND

H&

EP

AS

P B S H D M H D M + F h H D M -1 (2 5 µ g )

P B S H D M H D M +F hH D M -1 (2 5 µ g )

0

1

2

3

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ay

Mu

cu

s S

co

re***

# # #

PBS HDM HDM +FhHDM-1 (25µg)

0

1

2

3

Lung

Infla

mm

atio

n Sc

ore ***

***###

181

IL-12p40 ND ND ND

IL-12p70 ND ND ND

IL-15 ND ND ND

IL-13 ND ND ND

RANTES 0.39 ± 0.09 0.84 ± 0.23 0.63 ± 0.16 NS

IL-9 50.94 ± 7.05 24.64 ± 4.10 24.29 ± 4.66 NS

Eotaxin 4.92 ± 1.03 15.29 ± 2.97 13.78 ± 4.81 NS

IL-17 0.07 ± 0.06 29.64 ± 13.11 5.62 ± 2.39 NS

IL-4 0.21 ± 0.08 15.64 ± 3.52 8.91 ± 3.28 NS

IL-22 0.65 ± 0.09 4.43 ± 0.78 2.31 ± 0.44 *

GM-CSF 0.29 ± 0.12 2.69 ± 0.93 0.50 ± 0.47 *

IL-6 0.16 ± 0.09 74.20 ± 21.45 20.69 ± 7.53 *

CCL2 (MCP-1) 0 4.79 ± 2.11 0 *

TNF 0.13 ± 0.04 2.94 ± 0.7 0.90 ± 0.30 **

IL-5 1.57 ± 0.29 61.81 ± 17.83 11.10 ± 3.12 **

CXCL1 (KC) 12.05 ± 1.51 120.71 ± 17.63 49.19 ± 11.61 ***

Data represent mean (pg/ml) ± SEM. *P < .05, **P < .01, ***P < .001 in house dust mite vs house dust mite + FhHDM-1 groups. N = 12 mice per group. ND, not detectable; NS, not significant.

Other research groups have identified parasite-derived proteins with therapeutic

activity in mouse models of asthma. The well-characterized of these parasite

proteins is ES-62, a glycoprotein secreted by the nematode Acanthocheilonema

vitea. Although effective in suppressing airway inflammation and features of

airway remodeling in a mouse model of ovalbumin (OVA) induced asthma, which

promotes eosinophilic inflammation, synthetic small molecule analogues of this

glycoprotein failed to demonstrate efficacy in clinically relevant models of allergic

asthma (6). Indeed, our data are the first to demonstrate efficacy of a parasite-

182

derived peptide in suppressing neutrophilic inflammation in response to clinically

relevant allergens. To validate our finding, we tested the efficacy of FhHDM-1 in

a model of LPS-induced neutrophilic inflammation. FhHDM-1 was administered

via intraperitoneal injection 24 h and 30 min prior to intratracheal delivery of LPS

(1mg/kg). In this model, treatment with FhHDM-1 also resulted in a significant

reduction in the number of neutrophils in BALF 6 h after LPS challenge

(Appendix).

DISCUSSION

Asthma is a complex and heterogeneous disease in which multiple molecular

pathways are at play. Current therapies based on inhaled corticosteroids are

effective in patients in which eosinophilic inflammation is a primary feature, but

have limited efficacy in patients with neutrophil-dominant inflammation, or mixed

granulocytic inflammation(5). Recent studies have identified the NLRP3

inflammasome as an important driver of neutrophilic inflammation in asthma(7).

Notably, however, the NLRP3 inflammasome also acts as transcriptional

regulator of T-helper 2 cell differentiation(8) which is critical to the development

of the eosinophilic inflammation. We have previously shown that FhHDM-1

inhibits lysosomal-associated NLRP3 inflammasome activation in murine and

human macrophages in vitro(2, 3). Thus, the protective effects of FhHDM-1

against mixed granulocytic inflammation may be attributed to its capacity to

impair the NLRP3 inflammasome(3). We did not detect increased levels of

secreted HMGB1 in BALF at the time point examined in this study (data not

shown). However, our transcriptomic studies indicated that FhHDM-1 inhibits

HMGB1 signalling. Since HMGB1 is released in response to inflammasome

183

activation in macrophages(9), FhHDM-1 may potentially modulate

inflammasome-dependent regulation of HMGB1 signalling in asthma. Certainly,

this is an important area for further research. In conclusion, the data support our

proposal that the immune modulatory activity of FhHDM-1 is sufficient to prevent

granulocytic inflammation and airway hyperreactivity in asthma, and provide a

compelling basis for its investigation as a novel therapeutic in this disease.


Synthesis of parasite peptides

FhHDM-1 and SmHDM-2 were synthesised to 95% purity, with trifluoroacetic acid

removed and verified to be endotoxin free (Genscript, USA).

Preparation and stimulation of bone-marrow derived macrophages

(BMDMs)

BALB/c and C57BL6 mice were purchased from the Australian Resource Centre

(Perth, Australia). All mice were housed under specific pathogen free conditions

and procedures were performed at the University of Technology Sydney (UTS),

under protocols compliant with the Australian Code for the Care and Use of

Animals for Scientific Purposes and approved by the UTS Animal Care and Ethics

Committee. Bone marrow cells isolated from BALB/c mice were differentiated for

6 d in RPMI 1640 supplemented with FBS (10%v/v), recombinant M-CSF (50

ng/ml; eBioscience, USA), 2-mercaptoethanol (50µM; Sigma Aldrich) and

Penicillin-Streptomycin (100U/ml). BMDMs were confirmed to be F4/80+ CD11b+

184

by flow cytometry. Cells were resuspended at 1x106 cells/mL and allowed to

adhere for 2 h. Cells were then treated with FhHDM-1 (15μM) for 1 h and/or

stimulated with LPS (from E. Coli, 0111.B4; Sigma Aldrich) at a concentration of

10 ng/ml, for 6 h or 24 h at 37˚C in 5% CO2.

Gene expression profiling and Ingenuity Pathway Analysis®

After removal of supernatants, cells were homogenised using TRIzol (Life

Technologies), as per the manufacturer’s protocol. The aqueous phase was then

transferred into a genomic DNA eliminating column from the RNeasy Mini Plus

kit (Qiagen). RNA was subsequently isolated as per the manufacturer’s

instructions. Gene expression was assessed using the Affymetrix Mouse Gene

2.1ST Array and performed at the Ramaciotti Centre for Genomics (University of

New South Wales, Australia). Analysis of fold changes in gene expression was

completed using Partek Genomics Suite (Partek Inc. USA). The generated data

files were grouped according to treatment (untreated, LPS or LPS+FhHDM-1),

and individual gene lists were generated by one way ANOVA comparison of

untreated vs LPS, and LPS vs LPS+FhHDM-1 at 6 h and 24 h time points (-2>fold-

change>2, P <0.05 with 5% false discovery rate). Generated gene lists were

further analysed using Ingenuity Pathway Analysis (IPA)® software (Ingenuity

Systems, Redwood City, CA), where a comparison analysis was conducted. The

analysis produced a list of canonical pathways that were assigned an activation

z-score, which infers the activation states of predicted transcriptional events as

either activated or inhibited.

185

Quantification of cytokines secreted by macrophages

After 24 h stimulation with LPS, supernatants of C57BL6 BMDMs were harvested

and the levels of secreted CCL2, IL-6 and TNF were quantified by ELISA (BD

Pharmingen, Australia).

Mouse model of allergic asthma

C57BL/6 mice were purchased from the Australian Resource Centre (Perth,

Australia). All mice were housed under specific pathogen free conditions and

procedures were performed at the University of Technology Sydney (UTS), under


Scientific Purposes and approved by the UTS Animal Care and Ethics

Committee. Mice (8 weeks of age) were sensitized to house dust mite allergen

(100μg) (Dermatophagoides pteronyssinus, Greer Laboratories, Lenoir, NC,

USA) intranasally. After 2 weeks, mice were challenged with house dust mite

(5μg) intranasally for 4 days (days 14-17). Control mice were sensitized and

challenged with PBS only. Synthetic FhHDM-1 (5, 10, 25μg), SmHDM-1 (25μg)

or PBS was administered by intravenous injection through the tail vein 30 min

prior to allergen challenge on days 14-17. Mice were exsanguinated with an

overdose of pentobarbital (100mg/kg) 24 h after the final allergen challenge on

day 18.

186

Analysis of Bronchoalveolar lavage fluid

The lungs were lavaged twice with 0.5mL sterile Hanks Balanced Salt Solution

(HBSS). The collected fluid was spun at 3000 rpm for 10 min at 4oC. Cell

supernatants were retained for analysis of cytokine/chemokine expression, while

cell pellets were resuspended in sterile HBSS for enumeration of total and

differential cell counts. To perform differential cell counts, cells were spun on

glass slides using a Cytospin 4 Cytocentrifuge (Thermo Fisher Scientific) and

were stained with Diff-Quik®. A total of 200 cells were counted to enumerate the

differential leukocyte count. Cytokine and chemokine concentrations in BALF

were measured using a customized MILLIPLEX® Multiplex Mouse

Cytokine/Chemokine assay (Millipore, Billerica, MA) according to manufacturer

instructions. The cytokines/chemokines measured were IL-25/IL-17E, IL-22, IL-

23, IL-33, eotaxin-1, GM-CSF, IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-9, IL-12 (p40), IL-

12 (p70), IL-13, IL-15, IL-17, KC, MCP-1, MIP-1α, RANTES and TNF. Each

sample was analyzed in duplicate using the MAGPIX® System. Five parameter

logistic regression was performed to predict the concentration of unknown

samples. HMGB1 was measured using a specific ELISA (IBL international)

according to manufacturer instructions.

Quantification of airway inflammation

Semi-quantitative scoring of airway inflammation (inflammatory cell infiltrate)

involved scoring the level of inflammatory cell infiltrates surrounding each airway.

Scores ranged from 0-4 (0: no inflammatory cell infiltrates around airway, 1: low

level cell infiltrates around part of airway, 2: moderate cell infiltrates around part

187

of or entire airway, 3: significant inflammatory cell infiltrates around part of or

entire airway, 4: airway completely surrounded by inflammatory cell infiltrates).

10 airways were scored per mouse. All sections were imaged on Aperio

Scanscope XT and Leica DM750 Brightfield microscope.

Quantification of mucus

Mucus producing cells were identified by Periodic acid-Schiff (PAS) staining and

scored from 0 to 5 based on percentage of PAS positive airway epithelial cells

(AEC) (0: 0% of total AEC, 1: 1-10% of total AEC, 2: 10-30% of total AEC, 3: 30-

50% of total AEC, 4: 50-80% of total AEC, 5: >80% of total AEC). 10 airways were

scored per mouse.

Airway hyperresponsiveness (AHR)

AHR was measured 24 h after the last allergen challenge by forced oscillation

technique using FlexiVent apparatus (SCIREQ, Montreal, Canada). Briefly, mice

were anesthetized using a cocktail of xylazine (0.2mg/10gm) and ketamine

(0.4mg/10gm body weight). An 18-gauge blunt needle was inserted into the

trachea and mice were kept under mechanical ventilation at 200 breaths/min with

a delivered tidal volume of 0.25 mL against a positive end-expiratory pressure

(PEEP) of 3 cm H2O. Total resistance (Rrs) and tissue resistance (Rn) were

recorded by administering increasing doses of nebulized methacholine (0 to 40

mg/mL) (Sigma-Aldrich, St Louis, MO, USA).

188

Mouse model of LPS induced neutrophilic inflammation

C57BL/6 female mice aged between 10-12 weeks were purchased from Envigo.

Housing and experimentation was carried out in accordance with the Animal

(Scientific Procedures) Act 1986 and current guidelines approved by the Queen’s

University Ethical Review Committee. FhHDM-1 (10µg) was administered via

intraperitoneal injection 24 h and 30 min prior to intratracheal delivery of

Pseudomonas LPS (1mg/kg; Sigma-Aldrich, Serotype 10, source strain ATCC

27316). Control mice were treated with PBS only. After 6 h, BALF was collected

and total and differential cell counts were performed.

Statistical Analysis

ANOVA for repeated measures was used to determine the levels of difference

between groups of mice. Significance levels were set at P = 0.05

189

REFERENCES

1. Robinson MW, Donnelly S, Hutchinson AT, To J, Taylor NL, Norton RS,

Perugini MA, Dalton JP. A Family of Helminth Molecules that Modulate Innate

Cell Responses via Molecular Mimicry of Host Antimicrobial Peptides. PLOS

Pathogens 2011; 7: e1002042.

2. Lund ME, Greer J, Dixit A, Alvarado R, McCauley-Winter P, To J, Tanaka A,

Hutchinson AT, Robinson MW, Simpson AM, O’Brien BA, Dalton JP, Donnelly

S. A parasite-derived 68-mer peptide ameliorates autoimmune disease in

murine models of Type 1 diabetes and multiple sclerosis. Scientific Reports

2016; 6: 37789.

3. Alvarado R, To J, Lund ME, Pinar A, Mansell A, Robinson MW, O’Brien BA,

Dalton JP, Donnelly S. The immune modulatory peptide FhHDM-1 secreted by

the helminth Fasciola hepatica prevents NLRP3 inflammasome activation by

inhibiting endolysosomal acidification in macrophages. The FASEB Journal

2017; 31: 85-95.

4. Ullah MA, Loh Z, Gan WJ, Zhang V, Yang H, Li JH, Yamamoto Y, Schmidt AM,

Armour CL, Hughes JM, Phipps S, Sukkar MB. Receptor for advanced


allergic airway sensitization and airway inflammation. Journal of Allergy and

Clinical Immunology 2014.

5. Chung KF. Targeting the interleukin pathway in the treatment of asthma. The

Lancet 2015; 386: 1086-1096.

6. Janicova L, Rzepecka J, Rodgers DT, Doonan J, Bell KS, Lumb FE, Suckling

CJ, Harnett MM, Harnett W. Testing small molecule analogues of the

Acanthocheilonema viteae immunomodulator ES-62 against clinically relevant

allergens. Parasite immunology 2016; 38: 340-351.

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7. Simpson JL, Phipps S, Baines KJ, Oreo KM, Gunawardhana L, Gibson PG.

Elevated expression of the NLRP3 inflammasome in neutrophilic asthma. The


8. Bruchard M, Rebe C, Derangere V, Togbe D, Ryffel B, Boidot R, Humblin E,

Hamman A, Chalmin F, Berger H, Chevriaux A, Limagne E, Apetoh L, Vegran

F, Ghiringhelli F. The receptor NLRP3 is a transcriptional regulator of TH2

differentiation. Nature immunology 2015; 16: 859-870.

9. Lu B, Nakamura T, Inouye K, Li J, Tang Y, Lundback P, Valdes-Ferrer SI,

Olofsson PS, Kalb T, Roth J, Zou Y, Erlandsson-Harris H, Yang H, Ting JP,

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191

Chapter 6

GENERAL DISCUSSION

192

GENERAL DISCUSSION

In this dissertation we have identified a role for RAGE as an early mediator of

cigarette-smoke induced airway inflammation and AHR which is relevant to

initiation of disease in COPD (Chapter 2). We have also demonstrated a

previously unrecognised role for the TLR4/RAGE signalling axis in severe

experimental asthma. Moreover, using a global phosphoproteomic approach, we

uncovered possible mechanisms by which this axis promotes corticosteroid-

resistant neutrophilic inflammation and AHR (Chapter 3). We have demonstrated

that MIF inhibition restores corticosteroid sensitivity in severe asthma via

regulation of annexin A1 (Chapter 4). Finally, our studies also identify FhHDM-1

as a possible pharmacological treatment for asthma (Chapter 5).

TLR4 and RAGE are major PRRs implicated in the pathogenesis of asthma and

COPD. Importantly, while our findings indicate that inhibition of co-operative

TLR4/RAGE signalling may be of therapeutic benefit in severe asthma, opposing

effects of TLR4 and RAGE signalling in a mouse model of acute cigarette-smoke

exposure suggests that inhibition of this signalling axis might be detrimental in

patients with COPD or asthma/COPD overlap. Although severe asthma and

COPD are considered to be separate disease entities, they share many common

features and may co-exist in individuals with asthma/COPD overlap (1-3). Indeed,

from the studies here, it is clear that inhibition of TLR4/RAGE signalling may not

be of benefit across the spectrum of disease phenotypes/endotypes in asthma

and COPD. Further studies in which the combined impact of TLR4/RAGE

inhibition in different disease models (eg asthma/COPD overlap) are required.

193

Loss of the protective effect against acute cigarette-smoke exposure in

TLR4/RAGE gene-deficient mice may be due to divergent roles of these

receptors in oxidant signalling. Notably, it has been shown that RAGE deficiency

leads to a decrease in thioredoxin reductase 1 (Txnrd 1) mRNA expression and

an associated reduction in cigarette-smoke induced oxidative stress and

emphysema in mice (4). As mentioned previously, TLR4 maintains the redox

balance by acting as a tonic repressor of NADPH oxidase (Nox) 3 and loss of

TLR4 leads to spontaneous emphysema in mice as a result of increased oxidant

generation (5). Furthermore, in the presence of cigarette smoke,TLR4 gene-

deletion leads to increased alveolar apoptosis and further emphysematous

changes (6) suggesting a protective role for TLR4 in COPD. Thus, further

investigations of the TLR4/RAGE signalling axis in disease models of

asthma/COPD as proposed above should incorporate a concomitant analysis of

oxidant signalling.

We have demonstrated that MIF inhibition restores corticosteroid sensitivity in

severe experimental asthma via regulation of annexin A1, although further

studies are needed to confirm this finding and to elucidate the underlying

mechanism. MIF counter-regulates the anti-inflammatory effects of

glucocorticoids via suppressing the glucocorticoid-induced expression of IκBα

(7), MKP-1 and GILZ (8, 9) and by enhancing the activation of downstream

signalling pathways such as ERK1/2, JNK, and p38 (10). Previous studies

demonstrated reduced corticosteroid-mediated induction of MKP-1 and GILZ in

alveolar macrophages (11) and airway smooth muscle cells (12), respectively, in

patients with severe asthma. Annexin A1 can act as an endogenous up-regulator

194

of MKP-1 to inhibit p38 MAPK activation (13). Thus, we propose that MIF

promotes corticosteroid-resistance by downregulating corticosteroid induced

anti-inflammatory genes such as annexin A1, MKP-1 and GILZ, leading to

increased activation of MAPKs in severe asthma; further studies are required to

test this mechanism.

Given we have identified a role for both MIF and TLR4/RAGE signalling in

mediating corticosteroid-resistant features of severe asthma, it is possible that

MIF lies upstream of TLR4/RAGE ligation. It has been shown that MIF promotes

the release of the TLR4/RAGE ligand HMGB1 from the nucleus to the

extracellular matrix as a result of increased ROS production and caveolin-1

phosphorylation in MCF-7 and MDA-MB-231 human breast cancer cell lines (14).

Also, other studies have shown that activation of protease activated receptor 4

(PAR4) induce the HMGB1 release in UROtsa cells that is mediated by MIF

(15). Moreover, previous studies have shown that rhHMGB1 induces the

expression of TLR4 and RAGE in alveolar macrophages and microvascular

endothelial cells, respectively (16, 17). Similarly, MIF has been shown to

enhance LPS-mediated TLR4 expression in macrophages (18). MIF, TLR4 and

RAGE activate similar downstream pathways including cytosolic phospholipase

A2 (PLA2) (19, 20), p38(21-23) and ERK kinases (24-26). Thus, we propose that

MIF, via induction of HMGB1 release, drives TLR4/RAGE signalling in severe

asthma; further studies are required to test this mechanism.

Finally, our studies identified FhHDM-1 as a possible pharmacological treatment

for asthma, however, further work is needed to test efficacy of this peptide in a

195

range of disease models, including chronic models of asthma. Significantly, as

we have shown that FhHDM-1 protects against airway neutrophilia, an important

next step is to determine if FhHDM-1 protects against corticosteroid-resistant

neutrophilic inflammation in experimental models of severe asthma and COPD. .

As previous studies have demonstrated that FhHDM-1 preferentially binds to

macrophages and modulates their capacity to reduce the secretion of pro-

inflammatory cytokines to alleviate the symptoms of different auto-immune

diseases (27), we propose that protective effects of FhHDM-1 in asthma may be

due to its capacity to modulate the activation of monocytes/macrophages in the

lung. Of note it has been shown that depletion of circulating monocytes protects

against allergic airway inflammation in house dust mite models of asthma, thus it

is possible that FhHDM-1 protects against asthma by preventing the

recruitment/and or activation of these cells in the lung(28).

LIMITATIONS

There are several limitations that should be acknowledged. As severe asthma is

a multifaceted heterogeneous disease, researchers have used appropriate

mouse models of severe asthma that mimics the specific phenotypes of the

disease to investigate the novel therapeutic interventions for treatment of the

severe asthma (29, 30). We are aware that we have used an acute model of the

corticosteroid resistant severe asthma characterized with neutrophilic

inflammation to understand the preliminary insights of the role of innate immune

receptors (Chapter 3) and MIF (Chapter 4) in the pathogenesis of severe

neutrophilic asthma. We are also aware that we have investigated the

196

prophylactic rather than the therapeutic intervention of the ISO-1, MIF inhibitor by

administering the ISO-1 30 minutes before and 6h after allergen challenge

(Chapter 4) in this acute model of severe neutrophilic asthma. While this model

reflects the neutrophilic phenotype of the human disease who responds poorly to

the corticosteroid treatment (31), further studies to validate the initial findings and

also to evaluate the therapeutic role of the ISO-1 are needed to perform in a

chronic model of severe asthma by increasing the allergen challenges that

encompass more of the features of the disease including airway remodeling and

persistent AHR (32). Investigating the therapeutic role of ISO-1 in a chronic model

will also help us to study the off-target effects of the ISO-1 as this compound

binds to the active site of the MIF that inhibits the tautomerase activity, which is

required for biological function (33).

Secondly, the use of the C57BL/6J strain mice, rather than BALB/c mice. We are

aware that BALB/c mice are considered to be the better strain for inducing the

models of asthma and COPD with robust airway inflammation when compared to

C57BL/6J mice (34-36) and might have the possibility of the impact on the

features of the disease model, however, due to lack of availability of gene-

manipulated BALB/c mice, we used C57BL/6J mice for developing the mouse

models of asthma and COPD.

Thirdly, due to time constraints, we used a single gender of mice (either female

or male) in the various studies. Therefore, our conclusions for each study cannot

be generalized to both genders, as disease pathology in asthma/COPD may be

influenced by gender-related factors (37-40).

197

In conclusion, the studies in this thesis have expanded our understanding of

innate immune mechanisms that underlie disease pathogenesis in asthma and

COPD, they have uncovered new targets for therapeutic intervention and have

identified a potential new treatment for asthma.

198

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204

APPENDICES

205

APPENDIX I: FhHDM-1 treatment altered genes in macrophages

from microarray analysis

gene_assignment Gene Symbol p-value(6h HDM/LPS vs. 6h LPS) Fold-Change(6h HDM/LPS vs. 6h LPS)NM_031168 // Il6 // interleukin 6 // 5 B1|5 15.7 cM // 16193 /// ENSMUST00000026845 // Il6 0.000352079 -187.713NM_001167828 // Trim30d // tripartite motif-containing 30D // 7 E3|7 // 209387 /// NM_1 Trim30d 6.06E-05 -172.152NM_010927 // Nos2 // nitric oxide synthase 2, inducible // 11 B5|11 46.74 cM // 18126 / Nos2 0.000420919 -145.317NM_010104 // Edn1 // endothelin 1 // 13 A4|13 20.82 cM // 13614 /// ENSMUST00000021796 Edn1 0.000158878 -90.6905NM_013730 // Slamf1 // signaling lymphocytic activation molecule family member 1 // 1 H Slamf1 0.000133758 -80.7479ENSMUST00000047498 // AA467197 // expressed sequence AA467197 // 2 E5|2 // 433470 /// N AA467197 5.04E-05 -76.2448NM_019494 // Cxcl11 // chemokine (C-X-C motif) ligand 11 // 5|5 E3 // 56066 /// NR_0381 Cxcl11 0.00662799 -66.6912NM_008599 // Cxcl9 // chemokine (C-X-C motif) ligand 9 // 5 E2|5 46.51 cM // 17329 /// Cxcl9 0.000917271 -60.712NM_001033415 // Shisa3 // shisa homolog 3 (Xenopus laevis) // 5 C3.1|5 // 330096 /// EN Shisa3 7.29E-05 -52.7708XR_378392 // Trim30c // tripartite motif-containing 30C // 7 E3|7 // 434219 /// ENSMUST Trim30c 3.57E-05 -52.5863NM_011331 // Ccl12 // chemokine (C-C motif) ligand 12 // 11 C|11 49.9 cM // 20293 /// E Ccl12 9.65E-05 -50.8604NM_001142706 // Cfb // complement factor B // 17 B1|17 18.41 cM // 14962 /// NM_008198 Cfb 0.00130591 -50.8015XM_003945749 // LOC630751 // interferon-inducible GTPase 1-like // --- // 630751 /// XR LOC630751 8.11E-05 -50.5806NM_001039647 // Gbp11 // guanylate binding protein 11 // 5 E5|5 // 634650 /// ENSMUST00 Gbp11 0.000167754 -49.824NM_008352 // Il12b // interleukin 12b // 11 A5-B2|11 25.94 cM // 16160 /// ENSMUST00000 Il12b 4.73E-05 -48.4816NM_008230 // Hdc // histidine decarboxylase // 2 E5-G|2 61.76 cM // 15186 /// ENSMUST00 Hdc 4.99E-05 -46.5621NM_009425 // Tnfsf10 // tumor necrosis factor (ligand) superfamily, member 10 // 3 A3|3 Tnfsf10 0.000322518 -42.0204NM_010554 // Il1a // interleukin 1 alpha // 2 F|2 62.9 cM // 16175 /// XM_006498793 // Il1a 0.0040839 -40.9628NM_001256005 // Gbp4 // guanylate binding protein 4 // 5 E5|5 50.68 cM // 17472 /// ENS Gbp4 0.000245878 -40.7457NM_011410 // Slfn4 // schlafen 4 // 11 C|11 // 20558 /// ENSMUST00000000208 // Slfn4 // Slfn4 0.0010104 -38.4837NM_011407 // Slfn1 // schlafen 1 // 11 C|11 50.3 cM // 20555 /// ENSMUST00000037994 // Slfn1 0.000520533 -33.5733NM_172648 // Ifi205 // interferon activated gene 205 // 1 H3|1 80.83 cM // 226695 /// E Ifi205 0.00349829 -33.4355ENSMUST00000090406 // BC094916 // cDNA sequence BC094916 // 1 H3|1 // 545384 /// ENSMUS BC094916 0.000112631 -33.3397ENSMUST00000128411 // Tgtp2 // T cell specific GTPase 2 // 11 B1.2|11 // 100039796 /// Tgtp2 0.00103599 -31.8747NM_011198 // Ptgs2 // prostaglandin-endoperoxide synthase 2 // 1 H1|1 63.84 cM // 19225 Ptgs2 0.000389719 -30.418NR_029565 // Mir155 // microRNA 155 // 16|16 // 387173 /// ENSMUST00000083463 // Mir155 Mir155 0.00364748 -30.263NM_009137 // Ccl22 // chemokine (C-C motif) ligand 22 // 8 C5|8 // 20299 /// ENSMUST000 Ccl22 5.79E-05 -29.9854NM_177371 // Tnfsf15 // tumor necrosis factor (ligand) superfamily, member 15 // 4 C1|4 Tnfsf15 0.000136493 -29.9763NM_009977 // Cst7 // cystatin F (leukocystatin) // 2|2 G1-G3 // 13011 /// ENSMUST000000 Cst7 9.58E-05 -29.8417NM_001110517 // Gm14446 // predicted gene 14446 // 19 C1|19 // 667373 Gm14446 2.70E-06 -29.3649NM_010720 // Lipg // lipase, endothelial // 18|18 E2 // 16891 /// ENSMUST00000066532 // Lipg 5.85E-05 -28.0617ENSMUST00000093501 // A530040E14Rik // RIKEN cDNA A530040E14 gene // 1 C5|1 // 621875 / A530040E14Rik 0.000267293 -25.9454NR_033483 // U90926 // cDNA sequence U90926 // 5 E2|5 // 57425 /// ENSMUST00000031356 / U90926 4.41E-06 -24.8312NM_001033339 // Mmp25 // matrix metallopeptidase 25 // 17 A3.3|17 // 240047 /// ENSMUST Mmp25 1.27E-05 -24.5774NM_001146275 // Iigp1 // interferon inducible GTPase 1 // 18 D3|18 // 60440 /// ENSMUST Iigp1 0.00112326 -23.7751NM_001083322 // Klrk1 // killer cell lectin-like receptor subfamily K, member 1 // 6 F3 Klrk1 6.91E-05 -23.5335NM_145636 // Il27 // interleukin 27 // 7 F3|7 // 246779 /// ENSMUST00000058429 // Il27 Il27 0.00182459 -23.3084XM_006527251 // Ms4a4c // membrane-spanning 4-domains, subfamily A, member 4C // 19 A|1 Ms4a4c 4.57E-05 -22.6564NM_032541 // Hamp // hepcidin antimicrobial peptide // 7 B1|7 19.27 cM // 84506 /// ENS Hamp 0.000274544 -21.915NM_001039646 // Gbp10 // guanylate-binding protein 10 // 5 E5|5 // 626578 /// ENSMUST00 Gbp10 0.000504264 -21.0164NM_001025606 // Tmem171 // transmembrane protein 171 // 13 D1|13 // 380863 /// ENSMUST0 Tmem171 5.75E-07 -20.5704NM_009452 // Tnfsf4 // tumor necrosis factor (ligand) superfamily, member 4 // 1 H2.1|1 Tnfsf4 0.000574162 -20.4869NM_026516 // Tmem178 // transmembrane protein 178 // 17 E3|17 // 68027 /// ENSMUST00000 Tmem178 1.38E-06 -19.5388NM_001159424 // Il12a // interleukin 12a // 3 E1|3 31.92 cM // 16159 /// NM_008351 // I Il12a 0.000184269 -17.6491NM_011246 // Rasgrp1 // RAS guanyl releasing protein 1 // 2 E5|2 59.19 cM // 19419 /// Rasgrp1 0.00123406 -16.9842NM_009728 // Atp10a // ATPase, class V, type 10A // 7 C|7 // 11982 /// XM_006540582 // Atp10a 1.28E-05 -16.6948NM_172603 // Phf11a // PHD finger protein 11A // 14 C3|14 // 219131 /// ENSMUST00000062 Phf11a 0.000272317 -16.569NM_008607 // Mmp13 // matrix metallopeptidase 13 // 9|9 A1-A2 // 17386 /// ENSMUST00000 Mmp13 3.24E-05 -16.5414XR_397994 // BC023105 // cDNA sequence BC023105 // 18 D3|18 // 667597 /// ENSMUST000000 BC023105 1.54E-05 -16.5019NM_001045543 // Heatr9 // HEAT repeat containing 9 // 11 C|11 // 629303 /// XM_00653390 Heatr9 6.72E-06 -16.3426NM_144548 // Il23r // interleukin 23 receptor // 6 C1|6 // 209590 /// ENSMUST0000011836 Il23r 3.24E-06 -16.2563NM_001037925 // BC147527 // cDNA sequence BC147527 // 13|13 // 625360 /// XM_006517732 BC147527 6.81E-06 -16.2362NM_009801 // Car2 // carbonic anhydrase 2 // 3 A1|3 3.23 cM // 12349 /// XM_006530050 / Car2 4.11E-05 -16.1024--- 6.91E-05 -16.0864NM_013654 // Ccl7 // chemokine (C-C motif) ligand 7 // 11 C|11 49.83 cM // 20306 /// EN Ccl7 4.21E-07 -15.3987NM_001045526 // Scimp // SLP adaptor and CSK interacting membrane protein // 11 B3|11 / Scimp 4.65E-06 -15.2661ENSMUST00000103463 // Ighv14-1 // immunoglobulin heavy variable 14-1 // --- // --- /// Ighv14-1 0.000113295 -15.1501NM_013652 // Ccl4 // chemokine (C-C motif) ligand 4 // 11 C|11 51.09 cM // 20303 /// EN Ccl4 0.000206747 -14.7649NM_007646 // Cd38 // CD38 antigen // 5 B3|5 23.85 cM // 12494 /// ENSMUST00000030964 // Cd38 0.00198458 -14.6528NM_009890 // Ch25h // cholesterol 25-hydroxylase // 19 C1|19 // 12642 /// ENSMUST000000 Ch25h 2.50E-06 -14.3695NM_177290 // Itgb8 // integrin beta 8 // 12 F2|12 // 320910 /// XM_006516016 // Itgb8 / Itgb8 0.00113658 -14.3692NM_011333 // Ccl2 // chemokine (C-C motif) ligand 2 // 11 C-E1|11 49.82 cM // 20296 /// Ccl2 6.36E-06 -14.3116NM_199016 // Enpp4 // ectonucleotide pyrophosphatase/phosphodiesterase 4 // 17 B3|17 // Enpp4 4.27E-06 -14.124NM_001205053 // Jdp2 // Jun dimerization protein 2 // 12|12 D3 // 81703 /// NM_030887 / Jdp2 3.66E-06 -13.8975NM_011693 // Vcam1 // vascular cell adhesion molecule 1 // 3 G1|3 50.17 cM // 22329 /// Vcam1 0.000608247 -13.693NM_001271498 // Il15ra // interleukin 15 receptor, alpha chain // 2 A1|2 8.97 cM // 161 Il15ra 5.84E-06 -13.5586NM_175026 // Pyhin1 // pyrin and HIN domain family, member 1 // 1 H3|1 // 236312 /// EN Pyhin1 0.000601279 -13.4304NM_001081746 // Gm7609 // predicted pseudogene 7609 // 1 C5|1 // 665378 /// NM_033616 / Gm7609 8.25E-07 -13.3772NM_175449 // Fam26f // family with sequence similarity 26, member F // 10 B1|10 // 2159 Fam26f 0.000197491 -13.3066NM_001081746 // Gm7609 // predicted pseudogene 7609 // 1 C5|1 // 665378 /// NM_033616 / Gm7609 2.69E-06 -13.251NM_001081746 // Gm7609 // predicted pseudogene 7609 // 1 C5|1 // 665378 /// NM_033616 / Gm7609 2.69E-06 -13.251NM_001013832 // Gpr31b // G protein-coupled receptor 31, D17Leh66b region // 17 A1|17 8 Gpr31b 7.55E-05 -13.0761ENSMUST00000103475 // Ighv14-4 // immunoglobulin heavy variable 14-4 // --- // --- /// Ighv14-4 3.67E-05 -12.8769NM_001168660 // Apol9b // apolipoprotein L 9b // 15 E1|15 // 71898 /// NM_173743 // Apo Apol9b 6.02E-05 -12.6713NM_001038643 // Slco3a1 // solute carrier organic anion transporter family, member 3a1 Slco3a1 1.68E-05 -12.5854NM_010846 // Mx1 // myxovirus (influenza virus) resistance 1 // 16 C4|16 57.46 cM // 17 Mx1 0.00229257 -12.4639NM_001101475 // F830016B08Rik // RIKEN cDNA F830016B08 gene // 18 D3|18 // 240328 /// X F830016B08Rik 0.000335906 -12.4454NM_145209 // Oasl1 // 2-5 oligoadenylate synthetase-like 1 // 5 F|5 // 231655 /// ENSMU Oasl1 0.000738364 -12.43NM_172777 // Gbp9 // guanylate-binding protein 9 // 5 E5|5 // 236573 /// XM_006534923 / Gbp9 6.84E-05 -12.3814ENSMUST00000057784 // Slc7a2 // solute carrier family 7 (cationic amino acid transporte Slc7a2 0.000307879 -11.9595NM_001242368 // F10 // coagulation factor X // 8 A1.1|8 5.73 cM // 14058 /// NM_007972 F10 1.01E-05 -11.9344NM_001033767 // Gm4951 // predicted gene 4951 // 18 D3|18 // 240327 /// ENSMUST00000031 Gm4951 0.0013424 -11.8381NM_001201367 // Tmem200b // transmembrane protein 200B // 4 D2.3|4 // 623230 /// ENSMUS Tmem200b 1.30E-07 -11.6745NM_001085502 // Nt5c1a // 5-nucleotidase, cytosolic IA // 4 D2.2|4 // 230718 /// XR_376 Nt5c1a 1.31E-05 -11.5855NM_001276248 // Cp // ceruloplasmin // 3|3 D // 12870 /// NM_001276250 // Cp // cerulop Cp 8.92E-06 -11.533ENSMUST00000127563 // Gm13822 // predicted gene 13822 // --- // --- Gm13822 0.000262329 -11.4441NM_008491 // Lcn2 // lipocalin 2 // 2 A3|2 22.09 cM // 16819 /// ENSMUST00000050785 // Lcn2 0.000189505 -11.351NM_010612 // Kdr // kinase insert domain protein receptor // 5 C3.3|5 40.23 cM // 16542 Kdr 8.36E-06 -11.1438NM_001034859 // Gm4841 // predicted gene 4841 // 18 D3|18 // 225594 /// ENSMUST00000090 Gm4841 0.000594742 -11.0274NM_010479 // Hspa1a // heat shock protein 1A // 17 B1|17 18.51 cM // 193740 /// ENSMUST Hspa1a 9.56E-06 -10.806--- 8.72E-06 -10.8042NM_001162883 // Apol9a // apolipoprotein L 9a // 15 E1|15 // 223672 /// NM_173786 // Ap Apol9a 5.66E-07 -10.6271

NM_009630 // Adora2a // adenosine A2a receptor // 10 B5.3|10 // 11540 /// XM_006513094 Adora2a 0.000866737 -10.4452NM_001081746 // Gm7609 // predicted pseudogene 7609 // 1 C5|1 // 665378 /// NM_033616 / Gm7609 1.15E-05 -10.4312NM_013606 // Mx2 // myxovirus (influenza virus) resistance 2 // 16 C4|16 57.51 cM // 17 Mx2 0.00078845 -10.3857ENSMUST00000173680 // Gm20481 // predicted gene 20481 // --- // --- /// BC054065 // Hsp Gm20481 6.49E-07 -10.2733NM_199015 // Phf11d // PHD finger protein 11D // 14 C3|14 31.48 cM // 219132 /// XM_006 Phf11d 3.15E-05 -10.1232NM_001289492 // Gbp3 // guanylate binding protein 3 // 3 H1|3 // 55932 /// NM_001289493 Gbp3 0.00656795 -10.0607ENSMUST00000134150 // Batf2 // basic leucine zipper transcription factor, ATF-like 2 // Batf2 6.39E-06 -9.95176NM_009742 // Bcl2a1a // B cell leukemia/lymphoma 2 related protein A1a // 9 E3.1|9 47.2 Bcl2a1a 0.000122452 -9.80143NM_001033335 // Serpina3f // serine (or cysteine) peptidase inhibitor, clade A, member Serpina3f 0.000138876 -9.72061NM_001164329 // Gm6904 // predicted gene 6904 // 14 C3|14 // 628693 /// ENSMUST00000168 Gm6904 4.58E-06 -9.5647NM_001025246 // Trp53i11 // transformation related protein 53 inducible protein 11 // 2 Trp53i11 1.10E-05 -9.26376NM_029639 // Plet1 // placenta expressed transcript 1 // 9|9 B // 76509 /// ENSMUST0000 Plet1 2.37E-06 -9.19854NM_010548 // Il10 // interleukin 10 // 1 E4|1 56.89 cM // 16153 /// ENSMUST00000016673 Il10 2.85E-06 -9.1824ENSMUST00000178021 // Ifitm7 // interferon induced transmembrane protein 7 // 16 A1|16 Ifitm7 6.73E-05 -9.0119XM_006498216 // Ptges // prostaglandin E synthase // 2 B|2 21.75 cM // 64292 /// NM_022 Ptges 0.000678447 -8.93959NM_010090 // Dusp2 // dual specificity phosphatase 2 // 2 F1|2 // 13537 /// ENSMUST0000 Dusp2 0.00104714 -8.91961NM_008360 // Il18 // interleukin 18 // 9 A5.3|9 27.75 cM // 16173 /// XM_006510023 // I Il18 1.96E-06 -8.90737NM_029612 // Slamf9 // SLAM family member 9 // 1 H3|1 // 98365 /// XM_006497067 // Slam Slamf9 1.87E-05 -8.89449NM_007535 // Bcl2a1c // B cell leukemia/lymphoma 2 related protein A1c // 9 F3|9 // 120 Bcl2a1c 0.000205658 -8.89343NM_001171007 // Nod1 // nucleotide-binding oligomerization domain containing 1 // 6 B3| Nod1 1.76E-06 -8.74022NM_001177349 // Pydc4 // pyrin domain containing 4 // 1 H3|1 // 623121 /// NM_001177350 Pydc4 4.05E-05 -8.67494NM_001164289 // Phf11c // PHD finger protein 11C // 14 C3|14 // 628705 /// ENSMUST00000 Phf11c 4.26E-05 -8.55533NM_001081746 // Gm7609 // predicted pseudogene 7609 // 1 C5|1 // 665378 /// ENSMUST0000 Gm7609 0.000440049 -8.5357NM_011909 // Usp18 // ubiquitin specific peptidase 18 // 6 F|6 57.17 cM // 24110 /// EN Usp18 0.000196903 -8.39555XR_400650 // LOC102634900 // uncharacterized LOC102634900 // --- // 102634900 /// ENSMU LOC102634900 4.41E-07 -8.38139--- 0.00158088 -8.35675NM_001291220 // Isg20 // interferon-stimulated protein // 7 D3|7 // 57444 /// NM_001113 Isg20 0.000253043 -8.32183--- 0.00580692 -8.3183NM_172796 // Slfn9 // schlafen 9 // 11 C|11 // 237886 /// ENSMUST00000038211 // Slfn9 / Slfn9 9.15E-05 -8.16161ENSMUST00000162784 // Gm16094 // predicted gene 16094 // --- // --- Gm16094 3.09E-05 -8.08667NM_001080813 // Rab11fip1 // RAB11 family interacting protein 1 (class I) // 8|8 A3 // Rab11fip1 9.29E-05 -8.04753ENSMUST00000137792 // Rsad2 // radical S-adenosyl methionine domain containing 2 // 12| Rsad2 0.00629878 -8.03369NM_009421 // Traf1 // TNF receptor-associated factor 1 // 2 B|2 // 22029 /// XM_0064978 Traf1 0.00221431 -8.0319--- 0.000914691 -8.02224NM_008867 // Pla2r1 // phospholipase A2 receptor 1 // 2 C1.1|2 // 18779 /// ENSMUST0000 Pla2r1 0.000355214 -7.9467NM_008204 // H2-M2 // histocompatibility 2, M region locus 2 // 17 B1|17 19.16 cM // 14 H2-M2 0.000420205 -7.94478--- 0.000770731 -7.89625NR_035466 // Mir1945 // microRNA 1945 // 16|16 6.4 cM // 100316833 /// ENSMUST000001579 Mir1945 0.000356706 -7.85203NM_153511 // Il1f9 // interleukin 1 family, member 9 // 2 A3|2 16.24 cM // 215257 /// E Il1f9 2.04E-05 -7.6936NM_001145827 // Stk40 // serine/threonine kinase 40 // 4 D2.2|4 // 74178 /// NM_028800 Stk40 5.49E-07 -7.6542NR_110420 // Ptgs2os2 // prostaglandin-endoperoxide synthase 2, opposite strand 2 // 1 Ptgs2os2 0.000566164 -7.59696NM_010276 // Gem // GTP binding protein (gene overexpressed in skeletal muscle) // 4 A1 Gem 5.39E-05 -7.56326NM_001033207 // Nlrc5 // NLR family, CARD domain containing 5 // 8 C5|8 // 434341 /// X Nlrc5 5.64E-05 -7.544NM_008013 // Fgl2 // fibrinogen-like protein 2 // 5 A3|5 9.83 cM // 14190 /// ENSMUST00 Fgl2 7.80E-05 -7.5175NM_008479 // Lag3 // lymphocyte-activation gene 3 // 6 F2|6 // 16768 /// ENSMUST0000003 Lag3 3.42E-06 -7.50915NM_001037917 // Gm6377 // predicted gene 6377 // X D|X // 622976 /// ENSMUST00000060013 Gm6377 1.48E-05 -7.50625--- 0.000927018 -7.48742NM_017370 // Hp // haptoglobin // 8 D3|8 57.11 cM // 15439 /// ENSMUST00000074898 // Hp Hp 1.75E-05 -7.46036ENSMUST00000023341 // Cd200 // CD200 antigen // 16 A1|16 29.53 cM // 17470 /// ENSMUST0 Cd200 7.43E-06 -7.44665NM_029472 // Gstt4 // glutathione S-transferase, theta 4 // 10 C1|10 // 75886 /// ENSMU Gstt4 1.86E-05 -7.41363NM_019450 // Il1f6 // interleukin 1 family, member 6 // 2 A3|2 16.26 cM // 54448 /// EN Il1f6 1.03E-07 -7.39034NR_040453 // Gm17757 // GTPase, very large interferon inducible 1 pseudogene // 7|7 // Gm17757 0.000125395 -7.33109NM_178890 // Abtb2 // ankyrin repeat and BTB (POZ) domain containing 2 // 2 E2|2 // 993 Abtb2 3.72E-08 -7.31221NM_016767 // Batf // basic leucine zipper transcription factor, ATF-like // 12 D2|12 // Batf 3.06E-06 -7.27959NM_001164059 // Sell // selectin, lymphocyte // 1 H2.2|1 71.37 cM // 20343 /// NM_01134 Sell 9.13E-07 -7.25382--- 0.000213685 -7.22871NM_001271603 // Socs1 // suppressor of cytokine signaling 1 // 16 A1|16 5.81 cM // 1270 Socs1 0.000308991 -7.16716NM_001271416 // Ly6a // lymphocyte antigen 6 complex, locus A // 15 D3|15 34.29 cM // 1 Ly6a 7.49E-08 -7.15985NM_010478 // Hspa1b // heat shock protein 1B // 17 B1|17 18.5 cM // 15511 /// ENSMUST00 Hspa1b 0.000153332 -7.14649NM_021443 // Ccl8 // chemokine (C-C motif) ligand 8 // 11 C|11 49.91 cM // 20307 /// EN Ccl8 4.14E-05 -7.12765XM_001473524 // Gm2427 // predicted gene 2427 // 1 C5|1 // 100039794 Gm2427 0.00238192 -7.10566NM_030701 // Hcar2 // hydroxycarboxylic acid receptor 2 // 5 F|5 // 80885 /// ENSMUST00 Hcar2 0.00329191 -7.04514NM_133664 // Lad1 // ladinin // 1 E4|1 // 16763 /// ENSMUST00000038760 // Lad1 // ladin Lad1 8.36E-07 -7.02736XM_006502252 // Rapgef2 // Rap guanine nucleotide exchange factor (GEF) 2 // 3 E3|3 // Rapgef2 2.65E-05 -7.02572ENSMUST00000180551 // Gm26584 // predicted gene, 26584 // --- // --- Gm26584 0.000136766 -7.00216NM_001002268 // Gpr126 // G protein-coupled receptor 126 // 10 A2|10 // 215798 /// ENSM Gpr126 2.21E-05 -6.99669NM_001039701 // Il1rn // interleukin 1 receptor antagonist // 2 A3|2 16.36 cM // 16181 Il1rn 2.04E-05 -6.96281NM_001164327 // Phf11b // PHD finger protein 11B // 14 C3|14 // 236451 /// ENSMUST00000 Phf11b 0.000450708 -6.89147NM_178759 // Timd4 // T cell immunoglobulin and mucin domain containing 4 // 11 B1.1|11 Timd4 0.000460409 -6.88102NR_040453 // Gm17757 // GTPase, very large interferon inducible 1 pseudogene // 7|7 // Gm17757 0.00015864 -6.84672ENSMUST00000110200 // Sntb1 // syntrophin, basic 1 // 15 D1|15 22.14 cM // 20649 /// BC Sntb1 4.40E-10 -6.79585--- 0.00403516 -6.78129ENSMUST00000103468 // Igh-V11 // immunoglobulin heavy chain (V11 family) // 12 F1|12 // Igh-V11 8.54E-05 -6.77336--- 0.000211601 -6.76834NM_183162 // Helz2 // helicase with zinc finger 2, transcriptional coactivator // 2 H4| Helz2 0.000202825 -6.73343NM_153287 // Csrnp1 // cysteine-serine-rich nuclear protein 1 // 9 F4|9 // 215418 /// X Csrnp1 2.15E-08 -6.70599NM_001083312 // Gbp7 // guanylate binding protein 7 // 3 H1|3 // 229900 /// NM_145545 / Gbp7 0.0045267 -6.70578NM_015811 // Rgs1 // regulator of G-protein signaling 1 // 1 F|1 62.56 cM // 50778 /// Rgs1 2.79E-07 -6.70249NM_008367 // Il2ra // interleukin 2 receptor, alpha chain // 2 A2-A3|2 8.91 cM // 16184 Il2ra 5.67E-05 -6.5894ENSMUST00000070435 // Fabp3-ps1 // fatty acid binding protein 3, muscle and heart, pseu Fabp3-ps1 1.39E-05 -6.55506NM_029495 // Epsti1 // epithelial stromal interaction 1 (breast) // 14 D3|14 // 108670 Epsti1 0.000107394 -6.52711NM_001254747 // Il15 // interleukin 15 // 8 C2|8 39.33 cM // 16168 /// NM_008357 // Il1 Il15 3.51E-05 -6.46136NM_001177471 // Gm15056 // predicted gene 15056 // 8 A2|8 // 100504014 /// ENSMUST00000 Gm15056 0.000258381 -6.45464--- 0.00210122 -6.41436--- 0.000445895 -6.40836NM_001081249 // Vcan // versican // 13 C3|13 45.5 cM // 13003 /// NM_001134474 // Vcan Vcan 4.10E-07 -6.39956NM_001008497 // P2ry14 // purinergic receptor P2Y, G-protein coupled, 14 // 3 D|3 28.96 P2ry14 4.77E-08 -6.38648NM_001290646 // Lhx2 // LIM homeobox protein 2 // 2 B|2 // 16870 /// NM_010710 // Lhx2 Lhx2 0.000142503 -6.35913NR_027919 // Bambi-ps1 // BMP and activin membrane-bound inhibitor, pseudogene (Xenopus Bambi-ps1 6.30E-05 -6.31234NM_026840 // Pdgfrl // platelet-derived growth factor receptor-like // 8 A4|8 // 68797 Pdgfrl 1.94E-07 -6.30366NM_001252600 // Irf7 // interferon regulatory factor 7 // 7 F5|7 // 54123 /// NM_001252 Irf7 0.000265784 -6.24885ENSMUST00000120997 // Rnd1 // Rho family GTPase 1 // 15 F1|15 // 223881 /// BC048531 // Rnd1 1.79E-05 -6.22523NM_001286062 // Angpt1 // angiopoietin 1 // 15 B3.1|15 16.69 cM // 11600 /// NM_009640 Angpt1 6.73E-06 -6.20891

NM_001177752 // Pfkfb3 // 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 // 2 A1 Pfkfb3 3.10E-06 -6.19588NM_001033780 // I830077J02Rik // RIKEN cDNA I830077J02 gene // 3 F2.2|3 // 433638 /// X I830077J02Rik 8.61E-09 -6.18071NM_001163440 // Mov10 // Moloney leukemia virus 10 // 3|3 F2 // 17454 /// NM_001163441 Mov10 3.37E-06 -6.09729NM_008332 // Ifit2 // interferon-induced protein with tetratricopeptide repeats 2 // 19 Ifit2 0.00613412 -6.08241NR_003507 // Oas1b // 2-5 oligoadenylate synthetase 1B // 5 F|5 60.64 cM // 23961 /// E Oas1b 3.95E-05 -6.0571NM_133501 // Ntng2 // netrin G2 // 2 B|2 19.57 cM // 171171 /// ENSMUST00000048455 // N Ntng2 1.79E-06 -6.05336ENSMUST00000060442 // Gpr85 // G protein-coupled receptor 85 // 6 A1|6 // 64450 /// NM_ Gpr85 0.000218572 -6.05227NM_001081187 // Htra4 // HtrA serine peptidase 4 // 8 A2|8 // 330723 /// ENSMUST0000008 Htra4 4.22E-05 -6.0049--- 0.00256689 -5.97279XM_006535862 // LOC100041708 // nuclear body protein SP140-like // 1|1 // 100041708 LOC100041708 0.00030833 -5.95034NM_201368 // Xkr8 // X Kell blood group precursor related family member 8 homolog // 4 Xkr8 7.02E-07 -5.94836ENSMUST00000082757 // Gm24149 // predicted gene, 24149 // --- // --- Gm24149 0.000469826 -5.88602NM_138648 // Olr1 // oxidized low density lipoprotein (lectin-like) receptor 1 // 6 F3| Olr1 0.000905739 -5.86485NM_001172205 // Arid5a // AT rich interactive domain 5A (MRF1-like) // 1 B|1 // 214855 Arid5a 1.10E-06 -5.86051--- 0.00478412 -5.85967NM_018738 // Igtp // interferon gamma induced GTPase // 11 B1.3|11 36.01 cM // 16145 // Igtp 0.000687588 -5.85232NM_172621 // Clic5 // chloride intracellular channel 5 // 17|17 C // 224796 /// XM_0065 Clic5 0.000133461 -5.85195NM_001243039 // Gm4070 // predicted gene 4070 // 7 E3|7 // 100042856 /// NM_029000 // G Gm4070 2.24E-05 -5.84478NM_001161798 // Mthfr // 5,10-methylenetetrahydrofolate reductase // 4 E2|4 78.67 cM // Mthfr 2.13E-07 -5.83239NM_027450 // Glipr2 // GLI pathogenesis-related 2 // 4 B1|4 // 384009 /// ENSMUST000000 Glipr2 2.34E-06 -5.78801ENSMUST00000068569 // Bcl2a1b // B cell leukemia/lymphoma 2 related protein A1b // 9 E3 Bcl2a1b 4.25E-06 -5.77873NM_010751 // Mxd1 // MAX dimerization protein 1 // 6 D1|6 37.75 cM // 17119 /// ENSMUST Mxd1 5.53E-06 -5.77106--- 0.000327208 -5.75527NM_007536 // Bcl2a1d // B cell leukemia/lymphoma 2 related protein A1d // 9 E3.1|9 // 1 Bcl2a1d 2.80E-05 -5.64471NM_126166 // Tlr3 // toll-like receptor 3 // 8|8 B2 // 142980 /// XM_006509278 // Tlr3 Tlr3 5.59E-06 -5.63035NM_009404 // Tnfsf9 // tumor necrosis factor (ligand) superfamily, member 9 // 17 D|17 Tnfsf9 0.0054702 -5.61702NM_001199733 // Daxx // Fas death domain-associated protein // 17 B1|17 17.98 cM // 131 Daxx 4.12E-05 -5.60431ENSMUST00000156081 // Gm12840 // predicted gene 12840 // --- // --- Gm12840 0.00052171 -5.60417NM_021394 // Zbp1 // Z-DNA binding protein 1 // 2 H3|2 // 58203 /// ENSMUST00000029018 Zbp1 0.000350719 -5.57807NM_001243039 // Gm4070 // predicted gene 4070 // 7 E3|7 // 100042856 /// NM_029000 // G Gm4070 0.000183133 -5.5615NM_029005 // Mlkl // mixed lineage kinase domain-like // 8|8 D3 // 74568 /// XM_0065314 Mlkl 2.90E-05 -5.55206ENSMUST00000112574 // Klf8 // Kruppel-like factor 8 // X F3|X // 245671 /// NM_173780 / Klf8 9.89E-05 -5.54461NM_001081427 // Flnb // filamin, beta // 14 A1|14 // 286940 /// NM_134080 // Flnb // fi Flnb 7.07E-06 -5.53354NM_001164566 // Spats2l // spermatogenesis associated, serine-rich 2-like // 1|1 C2 // Spats2l 0.000480249 -5.52726--- 0.00271712 -5.51996NM_007707 // Socs3 // suppressor of cytokine signaling 3 // 11 E2|11 // 12702 /// ENSMU Socs3 0.00213594 -5.49358NM_025658 // Ms4a4d // membrane-spanning 4-domains, subfamily A, member 4D // 19 A|19 / Ms4a4d 0.000109083 -5.46808NM_001252374 // Nt5c3 // 5-nucleotidase, cytosolic III // 6 B3|6 // 107569 /// XM_00650 Nt5c3 6.90E-05 -5.4597NM_001004762 // Pla2g4c // phospholipase A2, group IVC (cytosolic, calcium-independent) Pla2g4c 0.00016746 -5.43261NM_001141948 // Nmi // N-myc (and STAT) interactor // 2|2 C1 // 64685 /// NM_001141949 Nmi 3.03E-06 -5.38282ENSMUST00000145961 // Gm12764 // predicted gene 12764 // --- // --- Gm12764 4.38E-06 -5.37002NM_007719 // Ccr7 // chemokine (C-C motif) receptor 7 // 11 D|11 // 12775 /// XM_006532 Ccr7 0.000955136 -5.33796NM_145226 // Oas3 // 2-5 oligoadenylate synthetase 3 // 5 F|5 60.64 cM // 246727 /// EN Oas3 0.000114475 -5.30533NM_029809 // 2310014L17Rik // RIKEN cDNA 2310014L17 gene // 7 A1|7 // 381845 /// ENSMUS 2310014L17Rik 0.00036202 -5.29897NM_146786 // Olfr914 // olfactory receptor 914 // 9 A5|9 // 258782 /// ENSMUST000000577 Olfr914 7.49E-05 -5.29817NM_007981 // Acsl1 // acyl-CoA synthetase long-chain family member 1 // 8|8 B2 // 14081 Acsl1 0.00060057 -5.29736NM_007611 // Casp7 // caspase 7 // 19 D2|19 51.84 cM // 12369 /// ENSMUST00000026062 // Casp7 1.39E-05 -5.29503NM_001159402 // Upp1 // uridine phosphorylase 1 // 11|11 A1-2 // 22271 /// XM_006514667 Upp1 0.00128968 -5.29337ENSMUST00000161540 // Gm17017 // predicted gene 17017 // --- // --- Gm17017 4.76E-07 -5.25234NM_019440 // Irgm2 // immunity-related GTPase family M member 2 // 11 B1.3|11 // 54396 Irgm2 0.000170735 -5.25119NM_001164477 // Ifih1 // interferon induced with helicase C domain 1 // 2|2 C3 // 71586 Ifih1 0.000472853 -5.22645NR_037278 // Mir3095 // microRNA 3095 // 4|4 32.2 cM // 100526502 /// ENSMUST0000017555 Mir3095 1.44E-05 -5.22033NM_008869 // Pla2g4a // phospholipase A2, group IVA (cytosolic, calcium-dependent) // 1 Pla2g4a 1.35E-05 -5.20299NR_029527 // Mirlet7i // microRNA let7i // 10|10 // 387251 /// ENSMUST00000083472 // Mi Mirlet7i 0.00021497 -5.18986NM_021893 // Cd274 // CD274 antigen // 19|19 C2 // 60533 /// ENSMUST00000016640 // Cd27 Cd274 5.44E-05 -5.16336NM_013632 // Pnp // purine-nucleoside phosphorylase // 14 B-C1|14 26.31 cM // 18950 /// Pnp 5.01E-06 -5.15841NR_028589 // Gm14005 // predicted gene 14005 // 2 F1|2 // 100043424 /// NR_028590 // Gm Gm14005 3.66E-05 -5.15076--- 0.000446993 -5.1483ENSMUST00000181444 // Gm26589 // predicted gene, 26589 // --- // --- /// XR_379475 // L Gm26589 2.66E-06 -5.12128ENSMUST00000111253 // Setdb2 // SET domain, bifurcated 2 // 14 C3|14 // 239122 /// AK08 Setdb2 5.25E-06 -5.12089NM_001177576 // Slc25a22 // solute carrier family 25 (mitochondrial carrier, glutamate) Slc25a22 1.59E-07 -5.10755ENSMUST00000181565 // Gm26522 // predicted gene, 26522 // --- // --- Gm26522 0.000691473 -5.08544NM_027081 // Dennd6b // DENN/MADD domain containing 6B // 15 E3|15 // 69440 /// ENSMUST Dennd6b 2.75E-05 -5.07813NM_001293783 // Ddx60 // DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 // 8 B3.1|8 // 23431 Ddx60 0.000297328 -5.05199NM_011562 // Tdgf1 // teratocarcinoma-derived growth factor 1 // 9 F3|9 60.79 cM // 216 Tdgf1 0.000235678 -5.03946NM_139269 // Pla2g16 // phospholipase A2, group XVI // 19 A|19 // 225845 /// XM_0065269 Pla2g16 0.000101568 -5.0065NM_172488 // Lacc1 // laccase (multicopper oxidoreductase) domain containing 1 // 14 D3 Lacc1 7.78E-05 -4.98429NM_025992 // Herc6 // hect domain and RLD 6 // 6 C1|6 // 67138 /// ENSMUST00000031817 / Herc6 0.000141657 -4.96207NM_001082552 // Trim21 // tripartite motif-containing 21 // 7 F1|7 // 20821 /// NM_0092 Trim21 5.02E-05 -4.95933NM_008380 // Inhba // inhibin beta-A // 13 A1|13 5.85 cM // 16323 /// ENSMUST0000004260 Inhba 1.21E-05 -4.91558NM_001135115 // Gm12250 // predicted gene 12250 // 11 B1.3|11 // 631323 Gm12250 0.000729117 -4.91256NM_028935 // Zfp558 // zinc finger protein 558 // 9|9 A3 // 72230 /// XM_006510619 // Z Zfp558 0.000734403 -4.90742NR_029457 // G530011O06Rik // RIKEN cDNA G530011O06 gene // X and Y|X // 654820 /// ENS G530011O06Rik 3.10E-06 -4.89865--- 7.93E-05 -4.89843NM_009829 // Ccnd2 // cyclin D2 // 6 F3|6 61.92 cM // 12444 /// ENSMUST00000000188 // C Ccnd2 2.51E-08 -4.88981--- 0.00554253 -4.88745NM_172734 // Stk38l // serine/threonine kinase 38 like // 6 G3|6 // 232533 /// XM_00650 Stk38l 4.45E-06 -4.88482NM_007413 // Adora2b // adenosine A2b receptor // 11 B2|11 // 11541 /// ENSMUST00000018 Adora2b 3.31E-05 -4.88111NM_015783 // Isg15 // ISG15 ubiquitin-like modifier // 4 E2|4 // 100038882 /// ENSMUST0 Isg15 0.00533423 -4.87357--- 0.00512395 -4.85417ENSMUST00000101477 // Peli1 // pellino 1 // 11 A3.2|11 13.81 cM // 67245 /// AF302503 / Peli1 6.37E-07 -4.83994XM_006496589 // LOC101056250 // sp110 nuclear body protein-like // --- // 101056250 /// LOC101056250 3.98E-05 -4.8312XM_006535876 // LOC677525 // sp110 nuclear body protein-like // 1|1 // 677525 /// NM_03 LOC677525 3.69E-05 -4.82202NM_175648 // Trim30b // tripartite motif-containing 30B // 7 E3|7 // 244183 /// ENSMUST Trim30b 8.67E-05 -4.81769ENSMUST00000129913 // Igf2bp2 // insulin-like growth factor 2 mRNA binding protein 2 // Igf2bp2 3.50E-07 -4.80765NM_001025395 // Src // Rous sarcoma oncogene // 2 H1|2 78.35 cM // 20779 /// NM_009271 Src 2.48E-05 -4.77321NR_030671 // AW011738 // expressed sequence AW011738 // 4 E2|4 // 100382 /// ENSMUST000 AW011738 0.000975424 -4.77209NM_001290755 // Tlr7 // toll-like receptor 7 // X F5|X // 170743 /// NM_001290757 // Tl Tlr7 8.08E-09 -4.76301NM_001271676 // Ifi47 // interferon gamma inducible protein 47 // 11 B1.2|11 // 15953 / Ifi47 0.000716896 -4.749NR_040371 // Gm14023 // predicted gene 14023 // 2|2 62.9 cM // 100503468 /// ENSMUST000 Gm14023 0.000762208 -4.74806NM_029508 // Pcgf5 // polycomb group ring finger 5 // 19 C2|19 // 76073 /// XM_00652743 Pcgf5 2.85E-05 -4.72256NM_027711 // Iqgap2 // IQ motif containing GTPase activating protein 2 // 13 D1|13 50.2 Iqgap2 4.66E-07 -4.69286NM_008329 // Ifi204 // interferon activated gene 204 // 1 H3|1 80.63 cM // 15951 /// XM Ifi204 0.000624384 -4.68899

BC005693 // Hmgn3 // high mobility group nucleosomal binding domain 3 // 9|9 E3.1 // 94 Hmgn3 6.77E-06 -4.68861NM_001162925 // Nudt17 // nudix (nucleoside diphosphate linked moiety X)-type motif 17 Nudt17 4.63E-05 -4.68102ENSMUST00000180798 // Gm26905 // predicted gene, 26905 // --- // --- Gm26905 0.0046274 -4.67329NM_011141 // Pou3f1 // POU domain, class 3, transcription factor 1 // 4 D2.2|4 57.86 cM Pou3f1 0.000148617 -4.64237ENSMUST00000028141 // 6530402F18Rik // RIKEN cDNA 6530402F18 gene // --- // --- /// ENS 6530402F18Rik 9.53E-06 -4.62851ENSMUST00000120177 // Gstt1 // glutathione S-transferase, theta 1 // 10 B5-C1|10 38.58 Gstt1 2.87E-06 -4.62694NR_038025 // 4933412E12Rik // RIKEN cDNA 4933412E12 gene // 10|10 // 71086 /// NR_03802 4933412E12Rik 0.000235683 -4.61796NM_172203 // Nox1 // NADPH oxidase 1 // X E3|X 55.69 cM // 237038 /// ENSMUST0000003361 Nox1 5.21E-06 -4.6179NM_019963 // Stat2 // signal transducer and activator of transcription 2 // 10 D3|10 76 Stat2 6.16E-05 -4.61444NM_011546 // Zeb1 // zinc finger E-box binding homeobox 1 // 18 A1|18 4.42 cM // 21417 Zeb1 9.62E-05 -4.59971NM_213615 // A530032D15Rik // RIKEN cDNA A530032D15Rik gene // 1 C5|1 // 381287 /// ENS A530032D15Rik 4.29E-06 -4.59379ENSMUST00000121995 // Gm15821 // predicted gene 15821 // 17|17 17.98 cM // 100502931 // Gm15821 4.34E-05 -4.59208NM_027320 // Ifi35 // interferon-induced protein 35 // 11 D|11 // 70110 /// ENSMUST0000 Ifi35 1.62E-05 -4.58659NR_002687 // Gm5424 // argininosuccinate synthase pseudogene // 10 B4|10 // 432466 /// Gm5424 0.000737055 -4.57913--- 0.00435346 -4.56614XM_006496589 // LOC101056250 // sp110 nuclear body protein-like // --- // 101056250 /// LOC101056250 1.76E-05 -4.55863NM_001162412 // Cysltr2 // cysteinyl leukotriene receptor 2 // 14 D3|14 // 70086 /// NM Cysltr2 1.34E-05 -4.53919NM_001083927 // Tle3 // transducin-like enhancer of split 3, homolog of Drosophila E(sp Tle3 1.67E-07 -4.53704NM_001293635 // Ktn1 // kinectin 1 // 14|14 C2 // 16709 /// NM_001293636 // Ktn1 // kin Ktn1 9.88E-06 -4.53071BC096584 // H2-Q5 // histocompatibility 2, Q region locus 5 // 17 B1|17 19.17 cM // 150 H2-Q5 3.10E-05 -4.51199BC096584 // H2-Q5 // histocompatibility 2, Q region locus 5 // 17 B1|17 19.17 cM // 150 H2-Q5 3.10E-05 -4.51199BC096584 // H2-Q5 // histocompatibility 2, Q region locus 5 // 17 B1|17 19.17 cM // 150 H2-Q5 3.10E-05 -4.51199NM_178395 // Zdhhc2 // zinc finger, DHHC domain containing 2 // 8 A4|8 // 70546 /// ENS Zdhhc2 3.45E-06 -4.50909NM_008102 // Gch1 // GTP cyclohydrolase 1 // 14 C2-3|14 24.6 cM // 14528 /// ENSMUST000 Gch1 1.93E-06 -4.50362NM_013875 // Pde7b // phosphodiesterase 7B // 10 A3|10 // 29863 /// XM_006512758 // Pde Pde7b 1.70E-07 -4.495NM_023738 // Uba7 // ubiquitin-like modifier activating enzyme 7 // 9 F2|9 59.07 cM // Uba7 9.97E-07 -4.48413NM_011530 // Tap2 // transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) // 17 Tap2 1.99E-08 -4.47195NM_001033632 // Ifitm6 // interferon induced transmembrane protein 6 // 7 F5|7 // 21300 Ifitm6 1.14E-05 -4.47168XR_378400 // Gm8995 // predicted gene 8995 // 7 E3|7 // 668139 /// ENSMUST00000184842 / Gm8995 2.21E-05 -4.46867NM_001008232 // Asap3 // ArfGAP with SH3 domain, ankyrin repeat and PH domain 3 // 4 D3 Asap3 3.74E-07 -4.45294NM_024495 // Car13 // carbonic anhydrase 13 // 3|3 A2 // 71934 /// ENSMUST00000029071 / Car13 2.44E-05 -4.44787NM_001102404 // Acp5 // acid phosphatase 5, tartrate resistant // 9 A3|9 8.38 cM // 114 Acp5 4.62E-06 -4.44028NM_181402 // Parp11 // poly (ADP-ribose) polymerase family, member 11 // 6 F3|6 // 1011 Parp11 4.46E-06 -4.43825NR_033498 // AI504432 // expressed sequence AI504432 // 3 F2.3|3 // 229694 /// ENSMUST0 AI504432 0.000751344 -4.43824--- 0.000861093 -4.43551NM_001013817 // Sp140 // Sp140 nuclear body protein // 1 C5|1 // 434484 /// NM_00103790 Sp140 9.77E-06 -4.43359NM_001085385 // 1600014C10Rik // RIKEN cDNA 1600014C10 gene // 7|7 B1 // 72244 /// ENSM 1600014C10Rik 6.26E-09 -4.42478NR_030251 // Mir483 // microRNA 483 // 7|7 // 723874 /// ENSMUST00000093631 // Mir483 / Mir483 0.000270092 -4.42354NR_030251 // Mir483 // microRNA 483 // 7|7 // 723874 /// ENSMUST00000093631 // Mir483 / Mir483 0.000270092 -4.42354NM_175236 // Adhfe1 // alcohol dehydrogenase, iron containing, 1 // 1 A2|1 // 76187 /// Adhfe1 9.73E-06 -4.40854ENSMUST00000157357 // Gm22224 // predicted gene, 22224 // --- // --- Gm22224 0.0043801 -4.40485NM_001177881 // Mfap3l // microfibrillar-associated protein 3-like // 8|8 B3.2 // 71306 Mfap3l 4.26E-06 -4.39165NR_045687 // Gm9895 // predicted gene 9895 // 19 C1|19 // 100503337 Gm9895 4.94E-06 -4.37974--- 0.00109652 -4.37243XM_006544847 // LOC102642448 // schlafen family member 13-like // --- // 102642448 /// LOC102642448 4.95E-06 -4.36149NM_025687 // Tex12 // testis expressed gene 12 // 9 A5.3|9 // 66654 /// ENSMUST00000034 Tex12 0.00160996 -4.3435NM_008608 // Mmp14 // matrix metallopeptidase 14 (membrane-inserted) // 14 C2|14 27.79 Mmp14 0.000361206 -4.33081NM_001267583 // Zfp811 // zinc finger protein 811 // 17 B1|17 // 240063 /// NM_183177 / Zfp811 0.00105391 -4.31184ENSMUST00000103466 // Ighv11-1 // immunoglobulin heavy variable 11-1 // --- // --- /// Ighv11-1 0.000151154 -4.28823NM_008871 // Serpine1 // serine (or cysteine) peptidase inhibitor, clade E, member 1 // Serpine1 5.11E-06 -4.27429NM_001289568 // Sass6 // spindle assembly 6 homolog (C. elegans) // 3|3 G2 // 72776 /// Sass6 5.43E-05 -4.26283NM_008207 // H2-T24 // histocompatibility 2, T region locus 24 // 17 B1|17 18.84 cM // H2-T24 6.83E-05 -4.24715NM_177861 // Tmem67 // transmembrane protein 67 // 4 A1|4 // 329795 /// NR_110955 // Tm Tmem67 5.78E-06 -4.24565NR_015474 // Il1bos // interleukin 1 beta, opposite strand // 2 F1|2 // 329514 /// ENSM Il1bos 0.000260637 -4.23952NM_001294138 // Gyk // glycerol kinase // X C-D|X 39.32 cM // 14933 /// NM_001294140 // Gyk 7.22E-06 -4.23646NR_045657 // 4933432I03Rik // RIKEN cDNA 4933432I03 gene // 14|14 // 71264 4933432I03Rik 0.000153114 -4.23502ENSMUST00000046739 // Ifi44l // interferon-induced protein 44 like // 3 H3|3 76.94 cM / Ifi44l 0.000289435 -4.22873NM_011249 // Rbl1 // retinoblastoma-like 1 (p107) // 2 H1|2 78.05 cM // 19650 /// ENSMU Rbl1 2.13E-08 -4.22489NR_110420 // Ptgs2os2 // prostaglandin-endoperoxide synthase 2, opposite strand 2 // 1 Ptgs2os2 8.15E-05 -4.2175NR_030719 // Gm8979 // very large inducible GTPase 1 pseudogene // 7 E3|7 // 668108 /// Gm8979 4.74E-05 -4.21646NM_001170853 // Mndal // myeloid nuclear differentiation antigen like // 1 H3|1 // 1000 Mndal 6.73E-05 -4.2156NM_001167983 // Sipa1l1 // signal-induced proliferation-associated 1 like 1 // 12 D1|12 Sipa1l1 4.26E-09 -4.21487--- 3.36E-05 -4.20886NM_009156 // Sepw1 // selenoprotein W, muscle 1 // 7|7 A2 // 20364 /// ENSMUST000000443 Sepw1 1.76E-06 -4.20745NM_008591 // Met // met proto-oncogene // 6 A2|6 7.83 cM // 17295 /// ENSMUST0000011544 Met 2.76E-05 -4.19892NM_178732 // Zfp324 // zinc finger protein 324 // 7 A1|7 // 243834 /// ENSMUST000000387 Zfp324 6.36E-05 -4.19159NM_009141 // Cxcl5 // chemokine (C-X-C motif) ligand 5 // 5 E1|5 44.78 cM // 20311 /// Cxcl5 0.000537866 -4.1824NM_198095 // Bst2 // bone marrow stromal cell antigen 2 // 8 B3.3|8 // 69550 /// ENSMUS Bst2 3.90E-06 -4.18027NM_011852 // Oas1g // 2-5 oligoadenylate synthetase 1G // 5 F|5 60.65 cM // 23960 /// E Oas1g 0.000123827 -4.17816--- 0.00545785 -4.17304NR_030719 // Gm8979 // very large inducible GTPase 1 pseudogene // 7 E3|7 // 668108 /// Gm8979 6.92E-05 -4.17154NM_001037713 // Xaf1 // XIAP associated factor 1 // 11 B4|11 // 327959 /// NM_001291153 Xaf1 3.28E-05 -4.16317NM_001033405 // Treml2 // triggering receptor expressed on myeloid cells-like 2 // 17 C Treml2 5.23E-05 -4.16294NM_144559 // Fcgr4 // Fc receptor, IgG, low affinity IV // 1 H3|1 78.53 cM // 246256 // Fcgr4 3.69E-08 -4.14764XM_006521741 // Cd86 // CD86 antigen // 16 B5|16 25.72 cM // 12524 /// BC013807 // Cd86 Cd86 0.000115539 -4.14325NM_001161730 // Tap1 // transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) // Tap1 5.23E-05 -4.12589NM_001013368 // E2f8 // E2F transcription factor 8 // 7 B4|7 // 108961 /// ENSMUST00000 E2f8 6.48E-06 -4.11278ENSMUST00000145914 // Gm15478 // predicted gene 15478 // --- // --- /// AK048962 // Gm1 Gm15478 3.97E-06 -4.11122NR_029807 // Mir222 // microRNA 222 // X|X // 723828 /// ENSMUST00000083537 // Mir222 / Mir222 0.000920813 -4.10368NM_008328 // Ifi203 // interferon activated gene 203 // 1 H3|1 80.76 cM // 15950 /// EN Ifi203 2.77E-05 -4.07869NM_001048207 // Gypc // glycophorin C // 18 B1|18 18.05 cM // 71683 /// ENSMUST00000174 Gypc 2.64E-06 -4.0724--- 0.0065885 -4.06973NM_001256096 // Dtx2 // deltex 2 homolog (Drosophila) // 5 G2|5 // 74198 /// NM_0012560 Dtx2 0.000178182 -4.06851--- 0.00668499 -4.06373NM_001163575 // Parp10 // poly (ADP-ribose) polymerase family, member 10 // 15 D3|15 // Parp10 2.67E-06 -4.04783NM_011409 // Slfn3 // schlafen 3 // 11 C|11 // 20557 /// XM_006532656 // Slfn3 // schla Slfn3 2.69E-05 -4.04706AK089726 // Trim30a // tripartite motif-containing 30A // 7 E3|7 55.69 cM // 20128 Trim30a 0.000510591 -4.04626--- 0.00392912 -4.04104NM_175523 // Ppm1k // protein phosphatase 1K (PP2C domain containing) // 6 B3|6 // 2433 Ppm1k 1.84E-05 -4.0145NM_001290801 // Mgat4a // mannoside acetylglucosaminyltransferase 4, isoenzyme A // 1 B Mgat4a 3.20E-05 -3.99824NM_013531 // Gnb4 // guanine nucleotide binding protein (G protein), beta 4 // 3|3 B // Gnb4 3.02E-06 -3.98418NM_009871 // Cdk5r1 // cyclin-dependent kinase 5, regulatory subunit 1 (p35) // 11 B5|1 Cdk5r1 8.02E-05 -3.96703NM_001048177 // Jak2 // Janus kinase 2 // 19 C1|19 23.73 cM // 16452 /// NM_008413 // J Jak2 0.000239512 -3.96316

NM_009767 // Chic1 // cysteine-rich hydrophobic domain 1 // X D|X 42.3 cM // 12212 /// Chic1 7.24E-06 -3.959NR_108021 // Gm16712 // predicted gene, 16712 // 17|17 29.08 cM // 100504333 /// ENSMUS Gm16712 0.000228532 -3.9501ENSMUST00000174654 // Gm20470 // predicted gene 20470 // --- // --- /// AK132823 // Kat Gm20470 8.13E-05 -3.94079--- 0.00275342 -3.92917NM_016979 // Prkx // protein kinase, X-linked // X A7.3|X // 19108 /// XM_006527909 // Prkx 3.47E-07 -3.92903NM_001161790 // Mefv // Mediterranean fever // 16 A1|16 2.18 cM // 54483 /// NM_0011617 Mefv 0.00611593 -3.92723NM_001013817 // Sp140 // Sp140 nuclear body protein // 1 C5|1 // 434484 /// ENSMUST0000 Sp140 0.00177009 -3.92169ENSMUST00000111314 // Adamts4 // a disintegrin-like and metallopeptidase (reprolysin ty Adamts4 0.000442148 -3.91309BC096584 // H2-Q5 // histocompatibility 2, Q region locus 5 // 17 B1|17 19.17 cM // 150 H2-Q5 9.62E-06 -3.89569NM_145949 // Ido2 // indoleamine 2,3-dioxygenase 2 // 8 A2|8 // 209176 /// ENSMUST00000 Ido2 6.27E-05 -3.88232NM_001267621 // Gfi1 // growth factor independent 1 // 5 F|5 52.23 cM // 14581 /// NM_0 Gfi1 4.83E-05 -3.8822NM_145944 // Ccdc25 // coiled-coil domain containing 25 // 14 D1|14 // 67179 /// ENSMUS Ccdc25 0.000147717 -3.8766NM_198862 // Nlgn2 // neuroligin 2 // 11 B3|11 // 216856 /// ENSMUST00000056484 // Nlgn Nlgn2 6.77E-06 -3.86487--- 0.00599608 -3.86246NM_133948 // Psip1 // PC4 and SFRS1 interacting protein 1 // 4 C3|4 // 101739 /// ENSMU Psip1 1.80E-07 -3.85946NM_001033136 // Rmdn3 // regulator of microtubule dynamics 3 // 2 E5|2 // 67809 /// ENS Rmdn3 1.63E-06 -3.85623NM_028270 // Aldh1b1 // aldehyde dehydrogenase 1 family, member B1 // 4|4 B2 // 72535 / Aldh1b1 4.16E-05 -3.83789NM_172659 // Slc2a6 // solute carrier family 2 (facilitated glucose transporter), membe Slc2a6 0.00335899 -3.83727NM_030150 // Dhx58 // DEXH (Asp-Glu-X-His) box polypeptide 58 // 11 D|11 63.52 cM // 80 Dhx58 6.29E-06 -3.83125--- 0.00387615 -3.82845--- 0.00387615 -3.82845NM_001113379 // Lrrc32 // leucine rich repeat containing 32 // 7 E2|7 53.86 cM // 43421 Lrrc32 1.97E-05 -3.81242NM_001033759 // Tmem2 // transmembrane protein 2 // 19 B|19 // 83921 /// NM_031997 // T Tmem2 4.60E-07 -3.80899NM_007865 // Dll1 // delta-like 1 (Drosophila) // 17 A2|17 8.95 cM // 13388 /// XM_0065 Dll1 0.000365618 -3.79213NM_207244 // Cd200r4 // CD200 receptor 4 // 16 B4|16 // 239849 /// XM_006522128 // Cd20 Cd200r4 3.59E-08 -3.79088--- 0.00529187 -3.79062--- 2.37E-05 -3.78994NM_001163590 // Stx11 // syntaxin 11 // 10 A1|10 // 74732 /// NM_029075 // Stx11 // syn Stx11 7.99E-05 -3.78563--- 7.78E-05 -3.77007NM_007936 // Epha4 // Eph receptor A4 // 1 C1-C5|1 39.55 cM // 13838 /// ENSMUST0000002 Epha4 4.05E-05 -3.76892--- 0.00563992 -3.768NM_153510 // Pilra // paired immunoglobin-like type 2 receptor alpha // 5 G2|5 // 23180 Pilra 1.03E-05 -3.76014NM_001040026 // Sco1 // SCO cytochrome oxidase deficient homolog 1 (yeast) // 11 B3|11 Sco1 3.68E-06 -3.75012--- 5.61E-05 -3.74479NM_009403 // Tnfsf8 // tumor necrosis factor (ligand) superfamily, member 8 // 4 C1|4 3 Tnfsf8 9.19E-06 -3.74418NM_001037294 // Alpk2 // alpha-kinase 2 // 18 E1|18 // 225638 /// ENSMUST00000035548 // Alpk2 3.37E-06 -3.73747NM_008842 // Pim1 // proviral integration site 1 // 17 A3.3|17 15.38 cM // 18712 /// EN Pim1 2.99E-05 -3.72892NM_175118 // Dusp28 // dual specificity phosphatase 28 // 1 D|1 // 67446 /// ENSMUST000 Dusp28 7.85E-05 -3.72886NM_017466 // Ccrl2 // chemokine (C-C motif) receptor-like 2 // 9 F|9 60.92 cM // 54199 Ccrl2 0.000331314 -3.72793NM_011633 // Traf5 // TNF receptor-associated factor 5 // 1 H6|1 97.11 cM // 22033 /// Traf5 1.01E-05 -3.72592NM_001289617 // Zyx // zyxin // 6 B2.1|6 // 22793 /// NM_001289619 // Zyx // zyxin // 6 Zyx 1.76E-06 -3.71016--- 4.97E-07 -3.70834--- 0.00189761 -3.70773NM_001190400 // Bend7 // BEN domain containing 7 // 2 A1|2 // 209645 /// NM_178663 // B Bend7 0.00032662 -3.70241NM_028523 // Dcbld2 // discoidin, CUB and LCCL domain containing 2 // 16 C1.2|16 // 733 Dcbld2 5.20E-05 -3.69869NM_001083616 // Cacna1d // calcium channel, voltage-dependent, L type, alpha 1D subunit Cacna1d 8.94E-06 -3.68725NM_030098 // Rnase6 // ribonuclease, RNase A family, 6 // 14 C1|14 // 78416 /// ENSMUST Rnase6 2.23E-06 -3.67559NM_021887 // Il21r // interleukin 21 receptor // 7|7 F4 // 60504 /// XM_006508097 // Il Il21r 2.74E-07 -3.66483NR_045367 // A630012P03Rik // RIKEN cDNA A630012P03 gene // X A5|X // 100504594 /// ENS A630012P03Rik 3.02E-05 -3.66089NM_027182 // Trip13 // thyroid hormone receptor interactor 13 // 13 C1|13 40.15 cM // 6 Trip13 2.55E-06 -3.65132ENSMUST00000160674 // Csprs // component of Sp100-rs // 8 B1.3|1 // 114564 /// ENSMUST0 Csprs 5.17E-05 -3.6468NM_008326 // Irgm1 // immunity-related GTPase family M member 1 // 11 B1.2|11 // 15944 Irgm1 2.29E-05 -3.63918ENSMUST00000139725 // Mitd1 // MIT, microtubule interacting and transport, domain conta Mitd1 5.41E-06 -3.61858ENSMUST00000071792 // 1110038F14Rik // RIKEN cDNA 1110038F14 gene // 15|15 E1 // 117171 1110038F14Rik 2.36E-06 -3.59961NM_001169131 // Papd7 // PAP associated domain containing 7 // 13 C1|13 35.55 cM // 210 Papd7 1.14E-05 -3.59615NM_001190846 // Kat2b // K(lysine) acetyltransferase 2B // 17 C|17 27.86 cM // 18519 // Kat2b 1.39E-05 -3.59283NM_011267 // Rgs16 // regulator of G-protein signaling 16 // 1 G3|1 65.43 cM // 19734 / Rgs16 2.49E-05 -3.59276NM_009223 // Snn // stannin // 16|16 A2 // 20621 /// ENSMUST00000089011 // Snn // stann Snn 2.05E-05 -3.58395ENSMUST00000136542 // Gm11772 // predicted gene 11772 // --- // --- Gm11772 0.000459847 -3.58012NM_172883 // Mfsd7a // major facilitator superfamily domain containing 7A // 5 F|5 // 2 Mfsd7a 1.65E-05 -3.57876NM_010398 // H2-T23 // histocompatibility 2, T region locus 23 // 17 B1|17 18.86 cM // H2-T23 6.06E-06 -3.57303NM_138682 // Lrrc4 // leucine rich repeat containing 4 // 6 A3.3|6 // 192198 /// ENSMUS Lrrc4 0.000131967 -3.57163NM_001004185 // Whamm // WAS protein homolog associated with actin, golgi membranes and Whamm 4.40E-07 -3.57055XM_006537281 // Psmb9 // proteasome (prosome, macropain) subunit, beta type 9 (large mu Psmb9 4.66E-06 -3.56895NM_001034909 // Gm6034 // predicted gene 6034 // 17 B1|17 // 547347 /// ENSMUST00000097 Gm6034 0.000760847 -3.56105NM_010426 // Foxf1 // forkhead box F1 // 8 E1|8 70.31 cM // 15227 /// ENSMUST0000018150 Foxf1 0.00256245 -3.55747--- 0.00414304 -3.55277NM_172893 // Parp12 // poly (ADP-ribose) polymerase family, member 12 // 6 B1|6 // 2437 Parp12 8.02E-05 -3.55152NM_001005863 // Mtus1 // mitochondrial tumor suppressor 1 // 8 A4|8 // 102103 /// NM_00 Mtus1 7.44E-06 -3.5477--- 0.00633483 -3.54407NM_026384 // Dgat2 // diacylglycerol O-acyltransferase 2 // 7|7 F1 // 67800 /// ENSMUST Dgat2 0.000131691 -3.53457ENSMUST00000122664 // n-R5s164 // nuclear encoded rRNA 5S 164 // --- // --- n-R5s164 0.00651714 -3.52837NM_001077189 // Fcgr2b // Fc receptor, IgG, low affinity IIb // 1 H3|1 78.02 cM // 1413 Fcgr2b 5.55E-07 -3.52699--- 4.23E-05 -3.52631NM_177034 // Apba1 // amyloid beta (A4) precursor protein binding, family A, member 1 / Apba1 4.47E-07 -3.5261NM_001045481 // Ifi203 // interferon activated gene 203 // 1 H3|1 80.76 cM // 15950 /// Ifi203 1.46E-05 -3.51904NM_001029984 // Fcrlb // Fc receptor-like B // 1 H3|1 // 435653 /// ENSMUST00000094337 Fcrlb 0.00120184 -3.50051--- 0.000979206 -3.49865ENSMUST00000142107 // Gm11626 // predicted gene 11626 // --- // --- Gm11626 0.00159462 -3.49577NM_009775 // Tspo // translocator protein // 15 E1|15 39.4 cM // 12257 /// ENSMUST00000 Tspo 7.77E-06 -3.49272NM_001198560 // H2-Q7 // histocompatibility 2, Q region locus 7 // 17 B1|17 18.67 cM // H2-Q7 0.00325206 -3.49216NM_145857 // Nod2 // nucleotide-binding oligomerization domain containing 2 // 8 C3|8 / Nod2 1.78E-05 -3.4916XM_006497081 // Gm16340 // predicted gene 16340 // 1|1 80.65 cM // 100504287 /// ENSMUS Gm16340 0.000244488 -3.49059NM_011332 // Ccl17 // chemokine (C-C motif) ligand 17 // 8 C5|8 46.85 cM // 20295 /// X Ccl17 0.00117385 -3.48474NM_001177602 // Ak4 // adenylate kinase 4 // 4 C6|4 46.84 cM // 11639 /// XM_006502684 Ak4 9.73E-06 -3.47559NM_001252503 // Aftph // aftiphilin // 11 A3.1|11 // 216549 /// NM_001290545 // Aftph / Aftph 5.66E-06 -3.47424NM_194346 // Rnf31 // ring finger protein 31 // 14 C3|14 // 268749 /// ENSMUST000000194 Rnf31 2.30E-06 -3.46745NM_025653 // 3110001I22Rik // RIKEN cDNA 3110001I22 gene // 16 A1|16 // 66598 /// NM_02 3110001I22Rik 7.49E-07 -3.46337--- 0.000981309 -3.46272NM_008327 // Ifi202b // interferon activated gene 202B // 1 H3|1 // 26388 /// NM_011940 Ifi202b 5.52E-05 -3.45974NR_040335 // D330050G23Rik // RIKEN cDNA D330050G23 gene // 2|2 // 320975 /// ENSMUST00 D330050G23Rik 8.48E-06 -3.45207NM_029250 // Etnk1 // ethanolamine kinase 1 // 6 G3|6 75.41 cM // 75320 /// ENSMUST0000 Etnk1 6.79E-07 -3.44906XR_401026 // A730011C13Rik // RIKEN cDNA A730011C13 gene // 3|3 // 319916 /// ENSMUST00 A730011C13Rik 7.36E-06 -3.44766

ENSMUST00000104150 // Gm23294 // predicted gene, 23294 // --- // --- Gm23294 0.000214984 -3.43798NM_133954 // Usb1 // U6 snRNA biogenesis 1 // 8 D1|8 // 101985 /// ENSMUST00000034245 / Usb1 2.13E-06 -3.43427NM_011345 // Sele // selectin, endothelial cell // 1 H2.2|1 71.35 cM // 20339 /// ENSMU Sele 0.000370597 -3.43261NM_009022 // Aldh1a2 // aldehyde dehydrogenase family 1, subfamily A2 // 9 D|9 39.85 cM Aldh1a2 8.13E-05 -3.43052NM_001271375 // Milr1 // mast cell immunoglobulin like receptor 1 // 11 E1|11 // 380732 Milr1 6.44E-06 -3.42807NM_001122680 // Pvrl4 // poliovirus receptor-related 4 // 1 H2|1 // 71740 /// NM_027893 Pvrl4 1.28E-05 -3.42304ENSMUST00000170385 // Ighd6-1 // immunoglobulin heavy diversity 6-1 // --- // --- /// E Ighd6-1 0.00584786 -3.4189ENSMUST00000170385 // Ighd6-1 // immunoglobulin heavy diversity 6-1 // --- // --- /// E Ighd6-1 0.00584786 -3.4189NM_145458 // Pxk // PX domain containing serine/threonine kinase // 14 A1|14 4.7 cM // Pxk 7.97E-09 -3.40909NR_045324 // Gm19705 // predicted gene, 19705 // 1 E4-F|1 59.94 cM // 100503460 /// NR_ Gm19705 0.000273411 -3.40608NM_001009940 // Il19 // interleukin 19 // 1 E4|1 // 329244 /// ENSMUST00000016668 // Il Il19 2.27E-05 -3.39631NM_013754 // Insl6 // insulin-like 6 // 19|19 C3 // 27356 /// ENSMUST00000052380 // Ins Insl6 1.71E-05 -3.39599--- 1.89E-05 -3.38964AK032092 // Sh3bgrl2 // SH3 domain binding glutamic acid-rich protein like 2 // 9 E2|9 Sh3bgrl2 1.35E-05 -3.38731NM_010186 // Fcgr1 // Fc receptor, IgG, high affinity I // 3 F2.1|3 41.72 cM // 14129 / Fcgr1 7.55E-07 -3.38617ENSMUST00000120059 // Gm5388 // predicted gene 5388 // --- // --- /// ENSMUST0000017552 Gm5388 0.00238214 -3.38566NM_145968 // Tagap // T cell activation Rho GTPase activating protein // 17 A1|17 // 72 Tagap 0.000563507 -3.38396NM_172409 // Fmnl2 // formin-like 2 // 2 C1.1|2 // 71409 /// XM_006498332 // Fmnl2 // f Fmnl2 3.80E-05 -3.37806NM_010531 // Il18bp // interleukin 18 binding protein // 7|7 F1 // 16068 /// ENSMUST000 Il18bp 6.61E-06 -3.37765AK035387 // Gm20559 // predicted gene, 20559 // 6 A1|6 // 330256 Gm20559 8.13E-06 -3.37511NR_029806 // Mir221 // microRNA 221 // X|X // 723827 /// ENSMUST00000083488 // Mir221 / Mir221 4.85E-05 -3.36949NM_030253 // Parp9 // poly (ADP-ribose) polymerase family, member 9 // 16 B3|16 // 8028 Parp9 4.35E-06 -3.36937NM_001284409 // Casp3 // caspase 3 // 8 B1.1|8 26.39 cM // 12367 /// NM_009810 // Casp3 Casp3 2.07E-05 -3.3688NM_001122675 // Zcchc2 // zinc finger, CCHC domain containing 2 // 1 E2.1|1 // 227449 / Zcchc2 2.22E-05 -3.35989NM_172812 // Htr2a // 5-hydroxytryptamine (serotonin) receptor 2A // 14 D2|14 39.37 cM Htr2a 0.000143057 -3.35961NR_045641 // F630111L10Rik // RIKEN cDNA F630111L10 gene // 3 D|3 // 320463 /// AK17084 F630111L10Rik 2.49E-06 -3.35715--- 0.000320498 -3.35654NM_133990 // Il13ra1 // interleukin 13 receptor, alpha 1 // X A3.3|X 20.49 cM // 16164 Il13ra1 5.01E-06 -3.35201NM_001040399 // Larp1b // La ribonucleoprotein domain family, member 1B // 3 B|3 // 214 Larp1b 0.000581695 -3.34336NM_013673 // Sp100 // nuclear antigen Sp100 // 1 C5|1 43.6 cM // 20684 /// XM_006529287 Sp100 2.98E-05 -3.34278--- 0.00315782 -3.32797--- 0.00010688 -3.31364NM_021457 // Fzd1 // frizzled homolog 1 (Drosophila) // 5 A1|5 2.61 cM // 14362 /// ENS Fzd1 0.000118896 -3.30526NM_001110824 // Foxp4 // forkhead box P4 // 17 C|17 // 74123 /// NM_001110825 // Foxp4 Foxp4 0.000233544 -3.30262ENSMUST00000093902 // Rnf213 // ring finger protein 213 // 11 E2|11 83.48 cM // 672511 Rnf213 0.000708944 -3.30192NM_007609 // Casp4 // caspase 4, apoptosis-related cysteine peptidase // 9 A1|9 2.46 cM Casp4 0.000385371 -3.30165--- 2.06E-05 -3.30089NM_027309 // Lysmd2 // LysM, putative peptidoglycan-binding, domain containing 2 // 9 D Lysmd2 1.58E-05 -3.29962NM_010484 // Slc6a4 // solute carrier family 6 (neurotransmitter transporter, serotonin Slc6a4 9.65E-06 -3.29811NM_001204910 // AI607873 // expressed sequence AI607873 // 1 H3|1 // 226691 /// ENSMUST AI607873 0.000576016 -3.29507NM_032396 // Kremen1 // kringle containing transmembrane protein 1 // 11 A1|11 // 84035 Kremen1 1.93E-05 -3.28598NM_028044 // Cnn3 // calponin 3, acidic // 3 G1|3 // 71994 /// ENSMUST00000029773 // Cn Cnn3 5.76E-08 -3.28496NM_001164202 // Gm8369 // predicted gene 8369 // 19 A|19 // 666926 /// XM_006527260 // Gm8369 0.00141198 -3.27457NM_001077509 // Tnfrsf9 // tumor necrosis factor receptor superfamily, member 9 // 4 E2 Tnfrsf9 0.000589909 -3.27292NR_045813 // 4930599N23Rik // RIKEN cDNA 4930599N23 gene // 6 B1|6 // 75379 /// ENSMUST 4930599N23Rik 0.00194008 -3.26974ENSMUST00000143099 // 6530409C15Rik // RIKEN cDNA 6530409C15 gene // 6 A3.2|6 // 76224 6530409C15Rik 0.000625762 -3.26855NM_001114679 // 9930111J21Rik1 // RIKEN cDNA 9930111J21 gene 1 // 11 B1.2|11 // 667214 9930111J21Rik1 2.30E-05 -3.25784NM_016811 // Dgka // diacylglycerol kinase, alpha // 10 D3|10 77.14 cM // 13139 /// XM_ Dgka 3.85E-07 -3.2503NM_001035228 // St3gal5 // ST3 beta-galactoside alpha-2,3-sialyltransferase 5 // 6|6 C3 St3gal5 9.63E-07 -3.24967NM_007808 // Cycs // cytochrome c, somatic // 6 B2.3|6 24.32 cM // 13063 /// ENSMUST000 Cycs 4.43E-05 -3.2407NM_007808 // Cycs // cytochrome c, somatic // 6 B2.3|6 24.32 cM // 13063 /// ENSMUST000 Cycs 4.43E-05 -3.2407NM_172689 // Ddx58 // DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 // 4 A5|4 // 230073 /// Ddx58 0.000125999 -3.24043ENSMUST00000141700 // Gm15987 // predicted gene 15987 // 6|6 63.11 cM // 100504591 /// Gm15987 0.000615914 -3.23461NM_001004157 // Scarf1 // scavenger receptor class F, member 1 // 11 B5|11 // 380713 // Scarf1 0.000115465 -3.2312NM_172697 // Prpf38a // PRP38 pre-mRNA processing factor 38 (yeast) domain containing A Prpf38a 3.46E-06 -3.2307NM_134102 // Pla1a // phospholipase A1 member A // 16 B4|16 26.83 cM // 85031 /// XM_00 Pla1a 0.000873725 -3.22399XM_006533108 // Rhbdf2 // rhomboid 5 homolog 2 (Drosophila) // 11 E2|11 // 217344 /// E Rhbdf2 2.88E-06 -3.22034NM_001143689 // H2-Q4 // histocompatibility 2, Q region locus 4 // 17 B1|17 18.65 cM // H2-Q4 0.000105771 -3.21475NR_033804 // Art2a-ps // ADP-ribosyltransferase 2a, pseudogene // 7 E3|7 54.6 cM // 118 Art2a-ps 0.000429599 -3.20972NM_029084 // Slamf8 // SLAM family member 8 // 1|1 H2 // 74748 /// ENSMUST00000065679 / Slamf8 0.000133449 -3.20908NM_172413 // Rap2c // RAP2C, member of RAS oncogene family // X A5|X // 72065 /// ENSMU Rap2c 6.84E-06 -3.20633NM_001048054 // Dusp16 // dual specificity phosphatase 16 // 6 G1|6 65.77 cM // 70686 / Dusp16 9.76E-06 -3.18591NM_019949 // Ube2l6 // ubiquitin-conjugating enzyme E2L 6 // 2|2 E1 // 56791 /// ENSMUS Ube2l6 3.43E-05 -3.18457NM_028287 // Zufsp // zinc finger with UFM1-specific peptidase domain // 10 B1|10 // 72 Zufsp 4.63E-07 -3.18412NM_175256 // Heg1 // HEG homolog 1 (zebrafish) // 16 B3|16 // 77446 /// XM_006522719 // Heg1 2.50E-05 -3.17632XM_006528554 // Armcx6 // armadillo repeat containing, X-linked 6 // X E3|X // 278097 / Armcx6 3.19E-05 -3.17292NM_145391 // Tapbpl // TAP binding protein-like // 6 F3|6 // 213233 /// XM_006505862 // Tapbpl 0.000267526 -3.16457XM_006505152 // Zfp800 // zinc finger protein 800 // 6 A3.2|6 // 627049 /// ENSMUST0000 Zfp800 5.36E-06 -3.16083NM_001166402 // Tnfaip3 // tumor necrosis factor, alpha-induced protein 3 // 10 A3|10 8 Tnfaip3 0.00179973 -3.15947NM_001012236 // Trex1 // three prime repair exonuclease 1 // 9 F2|9 // 22040 /// NM_011 Trex1 5.91E-05 -3.1579NM_001033450 // Mnda // myeloid cell nuclear differentiation antigen // 1 H3|1 // 38130 Mnda 0.00166299 -3.15542--- 0.00506365 -3.15449NM_001164071 // Tank // TRAF family member-associated Nf-kappa B activator // 2 C1.3|2 Tank 4.80E-06 -3.15432ENSMUST00000154924 // Pnpt1 // polyribonucleotide nucleotidyltransferase 1 // 11|11 A4 Pnpt1 6.31E-07 -3.15185NM_033322 // Lztfl1 // leucine zipper transcription factor-like 1 // 9 F|9 74.36 cM // Lztfl1 4.13E-05 -3.1475NM_011113 // Plaur // plasminogen activator, urokinase receptor // 7 A3|7 // 18793 /// Plaur 1.45E-06 -3.14472NM_145211 // Oas1a // 2-5 oligoadenylate synthetase 1A // 5 F|5 60.65 cM // 246730 /// Oas1a 0.000251383 -3.14027NM_183249 // Wfdc21 // WAP four-disulfide core domain 21 // 11 C|11 // 66107 /// ENSMUS Wfdc21 0.000193247 -3.13731NM_172393 // Aim1 // absent in melanoma 1 // 10 B2|10 23.14 cM // 11630 /// ENSMUST0000 Aim1 7.74E-07 -3.13414NM_010577 // Itga5 // integrin alpha 5 (fibronectin receptor alpha) // 15 F3|15 58.9 cM Itga5 5.53E-05 -3.12922NM_133921 // Nfxl1 // nuclear transcription factor, X-box binding-like 1 // 5|5 D // 10 Nfxl1 6.06E-06 -3.12885NM_007832 // Dck // deoxycytidine kinase // 5 E2|5 // 13178 /// ENSMUST00000031311 // D Dck 1.68E-05 -3.12427NM_010404 // Hap1 // huntingtin-associated protein 1 // 11 D|11 63.47 cM // 15114 /// N Hap1 1.36E-05 -3.12275NM_001168334 // Gm2799 // predicted gene 2799 // X A3.1|X // 100040482 /// ENSMUST00000 Gm2799 0.000302876 -3.10997NM_001160018 // Tor1aip1 // torsin A interacting protein 1 // 1 G3|1 // 208263 /// NM_0 Tor1aip1 6.32E-05 -3.10815NM_133821 // Phlpp1 // PH domain and leucine rich repeat protein phosphatase 1 // 1 E2. Phlpp1 1.22E-05 -3.10664NM_133737 // Lancl2 // LanC (bacterial lantibiotic synthetase component C)-like 2 // 6| Lancl2 1.51E-05 -3.10183ENSMUST00000116345 // Gm17193 // predicted gene 17193 // --- // --- Gm17193 6.99E-05 -3.09737NR_015514 // 9330175E14Rik // RIKEN cDNA 9330175E14 gene // 8 C5|8 // 320377 /// ENSMUS 9330175E14Rik 0.00098427 -3.08617NM_175088 // Mdfic // MyoD family inhibitor domain containing // 6 A1|6 // 16543 /// EN Mdfic 1.33E-06 -3.0789NR_024017 // 4930594C11Rik // G1 to S phase transition pseudogene // 1 B|1 // 77633 4930594C11Rik 0.0033487 -3.078NM_013673 // Sp100 // nuclear antigen Sp100 // 1 C5|1 43.6 cM // 20684 /// XM_006529287 Sp100 9.94E-06 -3.0719NM_145227 // Oas2 // 2-5 oligoadenylate synthetase 2 // 5 F|5 60.64 cM // 246728 /// XM Oas2 2.73E-05 -3.07071

NM_172722 // Naa25 // N(alpha)-acetyltransferase 25, NatB auxiliary subunit // 5 F|5 // Naa25 1.01E-07 -3.06807NM_028440 // Abracl // ABRA C-terminal like // 10 A3|10 // 73112 /// ENSMUST00000020002 Abracl 3.42E-05 -3.06498NM_138657 // Socs7 // suppressor of cytokine signaling 7 // 11 D|11 // 192157 /// XM_00 Socs7 4.63E-05 -3.06329NM_001130476 // Tpst1 // protein-tyrosine sulfotransferase 1 // 5|5 F-G1 // 22021 /// N Tpst1 0.000344248 -3.06023NM_001159543 // Dpp4 // dipeptidylpeptidase 4 // 2 C2-D|2 35.85 cM // 13482 /// NM_0100 Dpp4 0.00230129 -3.05845XM_006543523 // Gm7160 // predicted gene 7160 // 1 E2.1|1 // 635504 Gm7160 0.000179035 -3.05459ENSMUST00000111276 // Slamf7 // SLAM family member 7 // 1|1 H2 // 75345 /// AB196816 // Slamf7 5.48E-05 -3.05133ENSMUST00000125475 // Fam3b // family with sequence similarity 3, member B // 16 C4|16 Fam3b 2.45E-05 -3.04506NM_001135151 // Slc39a14 // solute carrier family 39 (zinc transporter), member 14 // 1 Slc39a14 4.33E-05 -3.04151NM_001033308 // Themis2 // thymocyte selection associated family member 2 // 4 D2.3|4 / Themis2 1.10E-07 -3.04032--- 0.00665058 -3.03969NM_001146348 // Eng // endoglin // 2 B|2 22.09 cM // 13805 /// NM_001146350 // Eng // e Eng 2.01E-06 -3.03803NM_029522 // Gpsm2 // G-protein signalling modulator 2 (AGS3-like, C. elegans) // 3 F3| Gpsm2 1.18E-05 -3.0354NM_011979 // Vnn3 // vanin 3 // 10 A2-B1|10 // 26464 /// ENSMUST00000020190 // Vnn3 // Vnn3 0.000325013 -3.03352NM_145523 // Gca // grancalcin // 2 C1.3|2 // 227960 /// ENSMUST00000028257 // Gca // g Gca 0.00101159 -3.02332NR_030440 // Mir674 // microRNA 674 // 2|2 // 732489 /// ENSMUST00000102421 // Mir674 / Mir674 0.000988427 -3.02093NM_029509 // Gbp8 // guanylate-binding protein 8 // 5 E5|5 // 76074 /// ENSMUST00000031 Gbp8 0.00039846 -3.02072NM_174850 // Micall2 // MICAL-like 2 // 5 G2|5 // 231830 /// ENSMUST00000044642 // Mica Micall2 0.00067038 -3.0133NM_001172160 // Flrt3 // fibronectin leucine rich transmembrane protein 3 // 2 F3|2 // Flrt3 0.00310483 -3.01089NM_007984 // Fscn1 // fascin homolog 1, actin bundling protein (Strongylocentrotus purp Fscn1 2.20E-05 -3.00947NM_009627 // Adm // adrenomedullin // 7 F1|7 57.7 cM // 11535 /// ENSMUST00000033054 // Adm 0.00126378 -3.00921NM_010585 // Itpr1 // inositol 1,4,5-trisphosphate receptor 1 // 6 E1-E2|6 49.74 cM // Itpr1 4.00E-06 -3.00803NM_001045540 // Gm12185 // predicted gene 12185 // 11 B1.2|11 // 620913 /// ENSMUST0000 Gm12185 0.00369464 -2.99914ENSMUST00000101295 // 9930111J21Rik2 // RIKEN cDNA 9930111J21 gene 2 // 11 B1.2|11 // 2 9930111J21Rik2 0.000294653 -2.9987NM_016846 // Rgl1 // ral guanine nucleotide dissociation stimulator,-like 1 // 1|1 G2 / Rgl1 2.18E-05 -2.99596NM_001005421 // Amica1 // adhesion molecule, interacts with CXADR antigen 1 // 9 A5.2|9 Amica1 1.48E-05 -2.98654NM_019423 // Elovl2 // elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, Elovl2 1.83E-05 -2.98557NM_172833 // Malt1 // mucosa associated lymphoid tissue lymphoma translocation gene 1 / Malt1 0.00460151 -2.98259NM_138952 // Ripk2 // receptor (TNFRSF)-interacting serine-threonine kinase 2 // 4 A2|4 Ripk2 4.75E-06 -2.98068NM_011163 // Eif2ak2 // eukaryotic translation initiation factor 2-alpha kinase 2 // 17 Eif2ak2 0.000168502 -2.9783--- 0.00143152 -2.97767ENSMUST00000144738 // Gm15726 // predicted gene 15726 // --- // --- Gm15726 2.04E-05 -2.9766ENSMUST00000181307 // Gm26902 // predicted gene, 26902 // --- // --- /// ENSMUST0000018 Gm26902 0.00356654 -2.97534NM_001040699 // Mtmr7 // myotubularin related protein 7 // 8|8 B1.2 // 54384 /// ENSMUS Mtmr7 3.15E-05 -2.97488NM_175687 // A230050P20Rik // RIKEN cDNA A230050P20 gene // 9 A3|9 // 319278 /// ENSMUS A230050P20Rik 3.02E-05 -2.97309NM_001267724 // Asb13 // ankyrin repeat and SOCS box-containing 13 // 13 A1|13 // 14268 Asb13 5.61E-06 -2.97173NM_173370 // Cds1 // CDP-diacylglycerol synthase 1 // 5 E4|5 // 74596 /// ENSMUST000000 Cds1 2.31E-06 -2.97152NM_178892 // Tiparp // TCDD-inducible poly(ADP-ribose) polymerase // 3 E1|3 // 99929 // Tiparp 1.09E-05 -2.96317NM_027490 // Dcp2 // DCP2 decapping enzyme homolog (S. cerevisiae) // 18 B3|18 // 70640 Dcp2 2.54E-05 -2.95816NM_027482 // 5730508B09Rik // RIKEN cDNA 5730508B09 gene // 3|3 H1 // 70617 /// ENSMUST 5730508B09Rik 0.00279222 -2.95267ENSMUST00000180685 // Gm26797 // predicted gene, 26797 // --- // --- Gm26797 0.00170428 -2.9513NM_001281934 // Pcsk7 // proprotein convertase subtilisin/kexin type 7 // 9 A5.2|9 25.3 Pcsk7 4.58E-05 -2.94543NM_011486 // Stat3 // signal transducer and activator of transcription 3 // 11 D|11 63. Stat3 2.48E-06 -2.94543NM_001081549 // Rcan1 // regulator of calcineurin 1 // 16 C4|16 53.6 cM // 54720 /// NM Rcan1 3.51E-06 -2.94509--- 0.00610434 -2.94443NM_023182 // Ctrl // chymotrypsin-like // 8 D3|8 53.06 cM // 109660 /// ENSMUST00000034 Ctrl 0.000585495 -2.94363NM_028603 // Zbtb8a // zinc finger and BTB domain containing 8a // 4 D2.2|4 // 73680 // Zbtb8a 2.05E-06 -2.94327ENSMUST00000110005 // Rin2 // Ras and Rab interactor 2 // 2 G1|2 // 74030 /// NM_028724 Rin2 4.29E-06 -2.94181NM_011835 // Katna1 // katanin p60 (ATPase-containing) subunit A1 // 10 A1|10 // 23924 Katna1 0.00236137 -2.93424NM_016758 // Rgs14 // regulator of G-protein signaling 14 // 13 B1|13 29.8 cM // 51791 Rgs14 0.000261458 -2.92946NM_178644 // Oaf // OAF homolog (Drosophila) // 9 A5.1|9 24.24 cM // 102644 /// ENSMUST Oaf 0.000100199 -2.92904NM_011854 // Oasl2 // 2-5 oligoadenylate synthetase-like 2 // 5 F|5 // 23962 /// ENSMUS Oasl2 8.81E-05 -2.91964NM_001025599 // Trim26 // tripartite motif-containing 26 // 17 B1|17 19.16 cM // 22670 Trim26 0.000142242 -2.91878NM_027314 // March5 // membrane-associated ring finger (C3HC4) 5 // 19 C2|19 // 69104 / Mar-05 4.17E-05 -2.91362NM_021430 // Rilpl1 // Rab interacting lysosomal protein-like 1 // 5|5 F // 75695 /// X Rilpl1 6.66E-07 -2.90529ENSMUST00000158447 // Gm24500 // predicted gene, 24500 // --- // --- Gm24500 0.00153043 -2.90352NM_001290707 // Pde10a // phosphodiesterase 10A // 17 A1|17 // 23984 /// NM_011866 // P Pde10a 0.000333274 -2.89956ENSMUST00000030025 // Nr4a3 // nuclear receptor subfamily 4, group A, member 3 // 4|4 B Nr4a3 0.000760406 -2.89816NM_008418 // Kcna3 // potassium voltage-gated channel, shaker-related subfamily, member Kcna3 0.000113443 -2.89687NM_001198560 // H2-Q7 // histocompatibility 2, Q region locus 7 // 17 B1|17 18.67 cM // H2-Q7 8.23E-05 -2.89627NM_023141 // Tor3a // torsin family 3, member A // 1 H1|1 // 30935 /// ENSMUST000000796 Tor3a 5.71E-05 -2.89584NM_133816 // Sh3bp4 // SH3-domain binding protein 4 // 1 D|1 // 98402 /// ENSMUST000000 Sh3bp4 2.29E-05 -2.89409--- 0.00189062 -2.88899--- 0.00343492 -2.88756NM_001033245 // Hk3 // hexokinase 3 // 13 B1|13 // 212032 /// NM_001206390 // Hk3 // he Hk3 5.21E-08 -2.88567NM_001164062 // Stat5a // signal transducer and activator of transcription 5A // 11 D|1 Stat5a 4.27E-05 -2.88342ENSMUST00000080694 // Gm5407 // predicted gene 5407 // --- // --- Gm5407 0.0059683 -2.88233NM_011930 // Clcn7 // chloride channel 7 // 17 A3.3|17 12.53 cM // 26373 /// ENSMUST000 Clcn7 9.23E-06 -2.88165ENSMUST00000111360 // LOC100041057 // nuclear body protein SP140-like // 1|1 // 1000410 LOC100041057 0.00559857 -2.87914NM_008655 // Gadd45b // growth arrest and DNA-damage-inducible 45 beta // 10 C1|10 39.7 Gadd45b 3.80E-05 -2.87576NM_010231 // Fmo1 // flavin containing monooxygenase 1 // 1 H1|1 70.34 cM // 14261 /// Fmo1 0.000151724 -2.87359NM_010597 // Kcnab1 // potassium voltage-gated channel, shaker-related subfamily, beta Kcnab1 1.42E-06 -2.87299NM_001013371 // Dtx3l // deltex 3-like (Drosophila) // 16 B3|16 // 209200 /// ENSMUST00 Dtx3l 4.10E-06 -2.87272NM_021604 // Agrn // agrin // 4 E2|4 88.55 cM // 11603 /// XM_006538496 // Agrn // agri Agrn 1.97E-06 -2.87231NM_178695 // Prrg4 // proline rich Gla (G-carboxyglutamic acid) 4 (transmembrane) // 2 Prrg4 3.73E-05 -2.87075NM_008466 // Kpna3 // karyopherin (importin) alpha 3 // 14 D1|14 // 16648 /// ENSMUST00 Kpna3 0.000175535 -2.85786--- 1.01E-05 -2.85751NM_023044 // Slc15a3 // solute carrier family 15, member 3 // 19|19 B // 65221 /// ENSM Slc15a3 2.78E-06 -2.85205NM_001013779 // Aim2 // absent in melanoma 2 // 1 H3|1 // 383619 /// XM_006496915 // Ai Aim2 3.01E-07 -2.84831--- 0.000479892 -2.84108ENSMUST00000109212 // Gm5431 // predicted gene 5431 // 11 B1.2|11 // 432555 Gm5431 0.000368291 -2.83857NM_198007 // Ascc3 // activating signal cointegrator 1 complex subunit 3 // 10 B3|10 // Ascc3 2.66E-05 -2.83653NR_045750 // Gm16675 // predicted gene, 16675 // 8|8 26.42 cM // 100503498 /// ENSMUST0 Gm16675 4.57E-05 -2.83423NM_011785 // Akt3 // thymoma viral proto-oncogene 3 // 1|1 H4-H6 // 23797 /// XM_006496 Akt3 2.69E-06 -2.83234ENSMUST00000032961 // Nupr1 // nuclear protein transcription regulator 1 // 7 F4|7 // 5 Nupr1 1.69E-05 -2.82846--- 5.86E-06 -2.82689--- 1.30E-05 -2.82541--- 0.00393222 -2.82483NM_001177369 // Nfkb2 // nuclear factor of kappa light polypeptide gene enhancer in B c Nfkb2 0.000452869 -2.82182NM_026438 // Ppa1 // pyrophosphatase (inorganic) 1 // 10 B4|10 32.25 cM // 67895 /// EN Ppa1 6.60E-07 -2.82124NM_010156 // Samd9l // sterile alpha motif domain containing 9-like // 6 A1-A2|6 1.76 c Samd9l 7.06E-06 -2.8199NM_001146308 // Dbnl // drebrin-like // 11 A1|11 3.87 cM // 13169 /// NM_001146309 // D Dbnl 2.51E-06 -2.81451ENSMUST00000086787 // Tcp10b // t-complex protein 10b // 17 A1|17 7.8 cM // 21462 /// E Tcp10b 0.00179069 -2.81369

ENSMUST00000172979 // H2-Q5 // histocompatibility 2, Q region locus 5 // 17 B1|17 19.17 H2-Q5 0.00166037 -2.81236NM_009914 // Ccr3 // chemokine (C-C motif) receptor 3 // 9 F|9 75.05 cM // 12771 /// EN Ccr3 0.00153383 -2.81185NM_001290475 // Tdrd7 // tudor domain containing 7 // 4 B1|4 // 100121 /// NM_146142 // Tdrd7 3.96E-06 -2.81041--- 0.000906269 -2.8103NM_001008700 // Il4ra // interleukin 4 receptor, alpha // 7 F3|7 68.94 cM // 16190 /// Il4ra 5.57E-07 -2.79727NM_001112705 // Tlk2 // tousled-like kinase 2 (Arabidopsis) // 11 E1|11 // 24086 /// NM Tlk2 2.73E-06 -2.79344--- 0.00103173 -2.79247NM_133819 // Ppp1r15b // protein phosphatase 1, regulatory (inhibitor) subunit 15b // 1 Ppp1r15b 8.80E-07 -2.79245NM_001136082 // Timeless // timeless circadian clock 1 // 10 D3|10 76.49 cM // 21853 // Timeless 5.38E-05 -2.78894NM_009546 // Trim25 // tripartite motif-containing 25 // 11 C|11 // 217069 /// ENSMUST0 Trim25 9.81E-06 -2.78856NM_001113569 // Stxbp1 // syntaxin binding protein 1 // 2 B|2 22.09 cM // 20910 /// NM_ Stxbp1 1.26E-05 -2.78785NM_009776 // Serping1 // serine (or cysteine) peptidase inhibitor, clade G, member 1 // Serping1 0.000591374 -2.78757NM_023248 // Sbds // Shwachman-Bodian-Diamond syndrome homolog (human) // 5 G1.3|5 // 6 Sbds 3.05E-07 -2.78703NM_001191008 // Sstr5 // somatostatin receptor 5 // 17 A3.3|17 12.62 cM // 20609 /// NM Sstr5 0.00144817 -2.785NM_001003950 // Rab3ip // RAB3A interacting protein // 10 D2|10 64.96 cM // 216363 /// Rab3ip 6.74E-06 -2.78464NM_001172117 // Hck // hemopoietic cell kinase // 2 H1|2 75.41 cM // 15162 /// NM_01040 Hck 0.000241876 -2.78393ENSMUST00000073080 // Cycs // cytochrome c, somatic // 6 B2.3|6 24.32 cM // 13063 Cycs 9.81E-05 -2.78055NM_028810 // Rnd3 // Rho family GTPase 3 // 2 C1.1|2 // 74194 /// ENSMUST00000017288 // Rnd3 3.20E-05 -2.77978NM_001081223 // Rbbp8 // retinoblastoma binding protein 8 // 18 A1|18 // 225182 /// NM_ Rbbp8 0.000110373 -2.77921NM_025821 // Carhsp1 // calcium regulated heat stable protein 1 // 16 A1|16 4.26 cM // Carhsp1 3.45E-05 -2.77454ENSMUST00000168554 // Gm5423 // predicted gene 5423 // --- // --- Gm5423 0.000937776 -2.7709--- 0.000592109 -2.76584NM_010171 // F3 // coagulation factor III // 3 G1|3 52.94 cM // 14066 /// ENSMUST000000 F3 0.00108515 -2.76493NM_001201341 // Msi2 // musashi RNA-binding protein 2 // 11 C|11 // 76626 /// NM_054043 Msi2 3.71E-05 -2.76003NM_010397 // H2-T22 // histocompatibility 2, T region locus 22 // 17 B1|17 18.87 cM // H2-T22 0.000230093 -2.75415NM_030694 // Ifitm2 // interferon induced transmembrane protein 2 // 7|7 F5 // 80876 // Ifitm2 0.000156028 -2.75311NM_001005846 // Mcoln2 // mucolipin 2 // 3 H2|3 // 68279 /// NM_026656 // Mcoln2 // muc Mcoln2 3.03E-06 -2.74461NM_007602 // Capn5 // calpain 5 // 7 E2|7 // 12337 /// XM_006507275 // Capn5 // calpain Capn5 3.33E-07 -2.74307NM_172839 // Ccnj // cyclin J // 19 C3|19 // 240665 /// ENSMUST00000025983 // Ccnj // c Ccnj 4.94E-05 -2.74249NM_001290822 // Pdpn // podoplanin // 4 E1|4 // 14726 /// NM_010329 // Pdpn // podoplan Pdpn 6.31E-07 -2.73661NM_008630 // Mt2 // metallothionein 2 // 8 C5|8 46.32 cM // 17750 /// ENSMUST0000003421 Mt2 0.00131595 -2.73021NM_031373 // Ogfr // opioid growth factor receptor // 2 H4|2 // 72075 /// ENSMUST000000 Ogfr 8.33E-07 -2.7299NM_001289926 // 2010111I01Rik // RIKEN cDNA 2010111I01 gene // 13 B3|13 // 72061 /// NR 2010111I01Rik 0.00117493 -2.72839NM_001159407 // B3gnt5 // UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5 B3gnt5 0.00279012 -2.72786NM_001081029 // Tmem243 // transmembrane protein 243, mitochondrial // 5 A1|5 // 652925 Tmem243 1.29E-05 -2.72728NM_001081162 // Slc4a11 // solute carrier family 4, sodium bicarbonate transporter-like Slc4a11 0.000312502 -2.72345NM_009982 // Ctsc // cathepsin C // 7|7 D3-E1.1 // 13032 /// ENSMUST00000032779 // Ctsc Ctsc 0.000249848 -2.7162NM_172282 // Tmco3 // transmembrane and coiled-coil domains 3 // 8 A1.1|8 // 234076 /// Tmco3 1.63E-06 -2.71428NM_001286226 // Cacnb3 // calcium channel, voltage-dependent, beta 3 subunit // 15 F1|1 Cacnb3 8.10E-05 -2.71221ENSMUST00000129498 // Mrpl27 // mitochondrial ribosomal protein L27 // 11 D|11 58.9 cM Mrpl27 0.00603813 -2.70878NM_008884 // Pml // promyelocytic leukemia // 9 B|9 31.63 cM // 18854 /// NM_178087 // Pml 1.55E-05 -2.70019NM_028808 // P2ry13 // purinergic receptor P2Y, G-protein coupled 13 // 3 D|3 // 74191 P2ry13 4.84E-06 -2.69992ENSMUST00000124513 // Gm15247 // predicted gene 15247 // --- // --- /// AK019053 // Gm1 Gm15247 0.000130137 -2.69064NM_207160 // Olfr519 // olfactory receptor 519 // 7 E3|7 // 277935 /// ENSMUST000000847 Olfr519 0.000383568 -2.68993NM_013640 // Psmb10 // proteasome (prosome, macropain) subunit, beta type 10 // 8 D3|8 Psmb10 0.000272 -2.68836NM_001163136 // Macc1 // metastasis associated in colon cancer 1 // 12 F2|12 // 238455 Macc1 0.000216823 -2.68798NM_013885 // Clic4 // chloride intracellular channel 4 (mitochondrial) // 4 D3|4 // 298 Clic4 0.000164696 -2.68737NM_001168684 // Tmcc3 // transmembrane and coiled coil domains 3 // 10 C2|10 // 319880 Tmcc3 0.000244854 -2.68398XM_986941 // Ms4a4a // membrane-spanning 4-domains, subfamily A, member 4A // 19 A|19 / Ms4a4a 3.55E-05 -2.6816NM_008990 // Pvrl2 // poliovirus receptor-related 2 // 7 A3|7 9.94 cM // 19294 /// ENSM Pvrl2 3.43E-05 -2.67659NM_031181 // Siglece // sialic acid binding Ig-like lectin E // 7 B2|7 // 83382 /// XM_ Siglece 0.000741507 -2.67122NM_001205313 // Stat1 // signal transducer and activator of transcription 1 // 1 C1.1|1 Stat1 0.000413468 -2.66534NM_197944 // Hsh2d // hematopoietic SH2 domain containing // 8 B3.3|8 // 209488 /// ENS Hsh2d 0.000138819 -2.66396NM_011890 // Sgcb // sarcoglycan, beta (dystrophin-associated glycoprotein) // 5 C3.3|5 Sgcb 4.91E-08 -2.6633NM_018866 // Cxcl13 // chemokine (C-X-C motif) ligand 13 // 5 E3|5 // 55985 /// ENSMUST Cxcl13 0.0023243 -2.66117NM_001204983 // Cep85l // centrosomal protein 85-like // 10|10 // 100038725 /// XM_0065 Cep85l 0.000177066 -2.66046NM_207636 // Fndc3a // fibronectin type III domain containing 3A // 14 D2|14 37.62 cM / Fndc3a 4.31E-06 -2.66011NM_019807 // Acpp // acid phosphatase, prostate // 9 F1|9 // 56318 /// NM_207668 // Acp Acpp 5.99E-05 -2.65937--- 0.00430703 -2.65557NM_013880 // Plcl2 // phospholipase C-like 2 // 17 C|17 // 224860 /// XM_006524150 // P Plcl2 8.39E-06 -2.65374NM_172593 // Mier3 // mesoderm induction early response 1, family member 3 // 13 D2.2|1 Mier3 4.93E-07 -2.64631NM_007544 // Bid // BH3 interacting domain death agonist // 6 F1|6 57.02 cM // 12122 // Bid 4.73E-05 -2.64376NM_148927 // Plekha4 // pleckstrin homology domain containing, family A (phosphoinositi Plekha4 0.000155163 -2.6432NM_001024624 // Cdkl5 // cyclin-dependent kinase-like 5 // X F4|X 73.95 cM // 382253 // Cdkl5 9.14E-05 -2.63964NM_001167991 // Hook2 // hook homolog 2 (Drosophila) // 8 C3|8 // 170833 /// NM_133255 Hook2 0.000535584 -2.63804NM_001253817 // Tmem184b // transmembrane protein 184b // 15 E1|15 // 223693 /// NM_001 Tmem184b 1.16E-06 -2.63139NM_001161774 // St3gal3 // ST3 beta-galactoside alpha-2,3-sialyltransferase 3 // 4|4 D1 St3gal3 5.36E-05 -2.6292NM_172668 // Lrp4 // low density lipoprotein receptor-related protein 4 // 2 E1|2 50.63 Lrp4 0.000188915 -2.62762NM_199195 // Bckdhb // branched chain ketoacid dehydrogenase E1, beta polypeptide // 9 Bckdhb 5.94E-06 -2.62493NM_133888 // Smpdl3b // sphingomyelin phosphodiesterase, acid-like 3B // 4 D2.3|4 // 10 Smpdl3b 0.000453956 -2.62294ENSMUST00000123363 // Gm16014 // predicted gene 16014 // --- // --- Gm16014 0.000530995 -2.62098NR_037271 // Mir3088 // microRNA 3088 // 2|2 19.38 cM // 100526498 /// ENSMUST000001750 Mir3088 0.00410039 -2.61785ENSMUST00000172796 // Gm20496 // predicted gene 20496 // --- // --- /// ENSMUST00000173 Gm20496 0.0035479 -2.61755NM_001033196 // Znfx1 // zinc finger, NFX1-type containing 1 // 2 H3|2 // 98999 /// ENS Znfx1 1.90E-05 -2.61267NM_054041 // Antxr1 // anthrax toxin receptor 1 // 6 D1|6 // 69538 /// XM_006506564 // Antxr1 3.06E-07 -2.61059NM_026115 // Hat1 // histone aminotransferase 1 // 2 C2|2 // 107435 /// ENSMUST00000028 Hat1 7.68E-06 -2.60917NM_011756 // Zfp36 // zinc finger protein 36 // 7 A3|7 16.72 cM // 22695 /// ENSMUST000 Zfp36 4.21E-05 -2.6044NM_001145924 // Msantd3 // Myb/SANT-like DNA-binding domain containing 3 // 4|4 B2 // 6 Msantd3 0.00128495 -2.60401--- 0.000680801 -2.60022ENSMUST00000157375 // Gm25493 // predicted gene, 25493 // --- // --- Gm25493 0.00197975 -2.59655NM_019636 // Tbc1d1 // TBC1 domain family, member 1 // 5 C3.1|5 // 57915 /// ENSMUST000 Tbc1d1 3.35E-05 -2.59412NM_007791 // Csrp1 // cysteine and glycine-rich protein 1 // 1 E4|1 // 13007 /// ENSMUS Csrp1 2.03E-06 -2.59185NM_001038587 // Adar // adenosine deaminase, RNA-specific // 3|3 F2 // 56417 /// NM_001 Adar 3.10E-06 -2.58922NM_008385 // Inpp5b // inositol polyphosphate-5-phosphatase B // 4 D2|4 57.89 cM // 163 Inpp5b 1.60E-07 -2.58506NM_177368 // Tmtc2 // transmembrane and tetratricopeptide repeat containing 2 // 10 D1| Tmtc2 0.000262898 -2.58497--- 0.00332048 -2.58291NM_008748 // Dusp8 // dual specificity phosphatase 8 // 7 F5|7 87.59 cM // 18218 /// EN Dusp8 0.00129386 -2.58105NM_013529 // Gfpt2 // glutamine fructose-6-phosphate transaminase 2 // 11 B1.2|11 29.9 Gfpt2 0.000378559 -2.57876--- 0.000157823 -2.57859NM_027890 // Susd2 // sushi domain containing 2 // 10|10 B5.3 // 71733 /// ENSMUST00000 Susd2 0.000129425 -2.57846NM_172785 // Zc3h12d // zinc finger CCCH type containing 12D // 10 A1|10 // 237256 /// Zc3h12d 0.000329003 -2.57572NM_020498 // Ly6i // lymphocyte antigen 6 complex, locus I // 15 D3|15 // 57248 /// ENS Ly6i 0.00118703 -2.57413XM_006514332 // Misp // mitotic spindle positioning // 10 C1|10 // 78906 /// XM_0065143 Misp 0.00097045 -2.57303

NM_007892 // E2f5 // E2F transcription factor 5 // 3 A1|3 // 13559 /// XM_006530051 // E2f5 0.000124627 -2.56904NM_177910 // Gmppb // GDP-mannose pyrophosphorylase B // 9 F2|9 // 331026 /// ENSMUST00 Gmppb 6.93E-05 -2.56749NM_001160181 // Tor1aip2 // torsin A interacting protein 2 // 1 G3|1 // 240832 /// NM_0 Tor1aip2 2.32E-05 -2.56739NM_011957 // Creb3l1 // cAMP responsive element binding protein 3-like 1 // 2 E1|2 // 2 Creb3l1 0.000360634 -2.56304--- 0.000570072 -2.56283NM_145619 // Parp3 // poly (ADP-ribose) polymerase family, member 3 // 9 F1|9 // 235587 Parp3 5.41E-06 -2.55938NM_023440 // Tmem86b // transmembrane protein 86B // 7 A1|7 // 68255 /// ENSMUST0000005 Tmem86b 0.0033071 -2.55835NM_001039537 // Lif // leukemia inhibitory factor // 11 A1-A2|11 2.94 cM // 16878 /// E Lif 0.000137818 -2.55526--- 2.51E-06 -2.55492AK052181 // Gm9883 // predicted gene 9883 // 19 C1|19 // 791409 Gm9883 8.02E-05 -2.5535AK052181 // Gm9883 // predicted gene 9883 // 19 C1|19 // 791409 Gm9883 8.02E-05 -2.5535NM_001081009 // Parp8 // poly (ADP-ribose) polymerase family, member 8 // 13 D2.3|13 65 Parp8 4.65E-06 -2.55263--- 0.00442567 -2.54895NM_001035532 // Akap2 // A kinase (PRKA) anchor protein 2 // 4 B3|4 // 11641 /// NM_001 Akap2 2.40E-05 -2.54216NM_178098 // 4930486L24Rik // RIKEN cDNA 4930486L24 gene // 13 B2|13 // 214639 /// ENSM 4930486L24Rik 0.00125454 -2.53976ENSMUST00000083829 // Gm23847 // predicted gene, 23847 // --- // --- Gm23847 0.0053704 -2.53823NM_028019 // Rnf135 // ring finger protein 135 // 11 B5|11 47.59 cM // 71956 /// ENSMUS Rnf135 4.50E-05 -2.53795NM_010169 // F2r // coagulation factor II (thrombin) receptor // 13 D1|13 50.21 cM // 1 F2r 0.000444757 -2.53655--- 0.00514864 -2.53618NM_001159393 // Irf1 // interferon regulatory factor 1 // 11 B1.3|11 32.0 cM // 16362 / Irf1 0.00192183 -2.53251--- 0.00676113 -2.53173NM_182806 // Gpr18 // G protein-coupled receptor 18 // 14 E5|14 65.86 cM // 110168 /// Gpr18 0.00403693 -2.53052NM_181732 // Aida // axin interactor, dorsalization associated // 1|1 // 108909 /// ENS Aida 2.67E-06 -2.52614NM_177855 // Med12l // mediator complex subunit 12-like // 3 D|3 // 329650 /// ENSMUST0 Med12l 0.00151203 -2.52248NM_026960 // Gsdmd // gasdermin D // 15|15 D3-E1 // 69146 /// XM_006521343 // Gsdmd // Gsdmd 8.52E-06 -2.52115ENSMUST00000175017 // Gm25026 // predicted gene, 25026 // --- // --- Gm25026 0.00199338 -2.51863NM_009808 // Casp12 // caspase 12 // 9 A1|9 2.46 cM // 12364 /// ENSMUST00000027009 // Casp12 0.000847428 -2.51778--- 0.00154045 -2.51761ENSMUST00000032815 // Nfkbib // nuclear factor of kappa light polypeptide gene enhancer Nfkbib 0.000240455 -2.51652ENSMUST00000163802 // Gm17139 // predicted gene 17139 // --- // --- Gm17139 0.00617342 -2.51333ENSMUST00000160445 // Gm16549 // predicted gene 16549 // --- // --- /// AK007062 // Fnd Gm16549 0.000116497 -2.51224NM_008927 // Map2k1 // mitogen-activated protein kinase kinase 1 // 9 C|9 34.55 cM // 2 Map2k1 2.92E-07 -2.51143NM_001164314 // Wars // tryptophanyl-tRNA synthetase // 12|12 F2 // 22375 /// NM_001164 Wars 2.76E-06 -2.50916NM_001289704 // Cflar // CASP8 and FADD-like apoptosis regulator // 1 C1.3|1 29.16 cM / Cflar 0.00142119 -2.50854NM_001099217 // Ly6c2 // lymphocyte antigen 6 complex, locus C2 // 15 D3|15 // 10004154 Ly6c2 0.00129226 -2.50822NM_028341 // Ttc39c // tetratricopeptide repeat domain 39C // 18|18 A2 // 72747 /// XM_ Ttc39c 5.96E-06 -2.5068NM_175401 // Fbxw17 // F-box and WD-40 domain protein 17 // 13 A5|13 // 109082 /// XM_0 Fbxw17 1.16E-07 -2.50592NR_045932 // Slfn5os // schlafen 5, opposite strand // 11 C|11 // 76392 /// ENSMUST0000 Slfn5os 5.37E-05 -2.50578ENSMUST00000067924 // Lrrc8c // leucine rich repeat containing 8 family, member C // 5 Lrrc8c 2.51E-05 -2.50246ENSMUST00000031264 // Plac8 // placenta-specific 8 // 5 E3|5 48.49 cM // 231507 /// ENS Plac8 0.000376718 -2.4996--- 0.00651262 -2.4982NM_009189 // Six1 // sine oculis-related homeobox 1 // 12 C3|12 30.34 cM // 20471 /// E Six1 0.000483679 -2.49804NM_011580 // Thbs1 // thrombospondin 1 // 2 F1-F3|2 59.34 cM // 21825 /// ENSMUST000000 Thbs1 5.76E-06 -2.49643ENSMUST00000083384 // Gm24099 // predicted gene, 24099 // --- // --- Gm24099 0.000256886 -2.49416NM_001159301 // Lgals9 // lectin, galactose binding, soluble 9 // 11 B5|11 // 16859 /// Lgals9 0.000260481 -2.49061NM_011521 // Sdc4 // syndecan 4 // 2 H3|2 85.16 cM // 20971 /// ENSMUST00000017153 // S Sdc4 0.00196069 -2.4905AK079938 // BE692007 // expressed sequence BE692007 // 19|19 8.44 cM // 100504727 /// X BE692007 0.00391186 -2.48947--- 9.26E-05 -2.48864NM_144905 // 6330416G13Rik // RIKEN cDNA 6330416G13 gene // 4 C1|4 // 230279 /// XM_006 6330416G13Rik 4.18E-05 -2.48765NM_001110254 // Zfp945 // zinc finger protein 945 // 17 A3.3|17 // 240041 /// NM_177358 Zfp945 0.000156425 -2.48507ENSMUST00000178911 // Gm8324 // predicted gene 8324 // --- // --- Gm8324 0.00209703 -2.48312--- 0.00214769 -2.48167NM_172647 // F11r // F11 receptor // 1 H2|1 79.43 cM // 16456 /// ENSMUST00000043839 // F11r 0.000303267 -2.47178NM_001048146 // Azi2 // 5-azacytidine induced gene 2 // 9 F3|9 // 27215 /// NM_00128650 Azi2 1.00E-08 -2.46941ENSMUST00000170390 // Irf1 // interferon regulatory factor 1 // 11 B1.3|11 32.0 cM // 1 Irf1 0.00226821 -2.46905NM_001289915 // Cd83 // CD83 antigen // 13 A4-5|13 21.6 cM // 12522 /// NM_009856 // Cd Cd83 2.58E-05 -2.46836XM_006510634 // Ubash3b // ubiquitin associated and SH3 domain containing, B // 9 A5.1| Ubash3b 6.35E-05 -2.45831NM_028381 // Ccdc94 // coiled-coil domain containing 94 // 17 D|17 // 72886 /// ENSMUST Ccdc94 8.45E-06 -2.45694NM_010742 // Ly6d // lymphocyte antigen 6 complex, locus D // 15 D3|15 34.27 cM // 1706 Ly6d 0.000394887 -2.45541ENSMUST00000034522 // Clmp // CXADR-like membrane protein // 9 A5.1|9 // 71566 /// NM_1 Clmp 7.20E-12 -2.45509NM_026001 // Rnaseh2b // ribonuclease H2, subunit B // 14 D1|14 // 67153 /// ENSMUST000 Rnaseh2b 0.000332382 -2.45507NM_028451 // Larp1 // La ribonucleoprotein domain family, member 1 // 11|11 B2 // 73158 Larp1 3.70E-05 -2.45499NR_051981 // H2-Q5 // histocompatibility 2, Q region locus 5 // 17 B1|17 19.17 cM // 15 H2-Q5 0.000981177 -2.45331ENSMUST00000112618 // Gpd2 // glycerol phosphate dehydrogenase 2, mitochondrial // 2 C1 Gpd2 0.000287649 -2.45172NM_001163489 // Sema4a // sema domain, immunoglobulin domain (Ig), transmembrane domain Sema4a 4.07E-08 -2.45132NR_037982 // 9330159M07Rik // RIKEN cDNA 9330159M07 gene // 9|9 // 319673 9330159M07Ri 0.00162507 -2.45025--- 0.000914561 -2.4501ENSMUST00000103922 // Gm22427 // predicted gene, 22427 // --- // --- Gm22427 2.41E-05 -2.44595NM_001145799 // Ctla2a // cytotoxic T lymphocyte-associated protein 2 alpha // 13 B2|13 Ctla2a 0.00568309 -2.44321XR_106025 // LOC100503338 // uncharacterized LOC100503338 // --- // 100503338 /// ENSMU LOC100503338 0.000330646 -2.44293NM_001163645 // Osbpl3 // oxysterol binding protein-like 3 // 6|6 B3 // 71720 /// NM_02 Osbpl3 5.41E-05 -2.44221NM_011347 // Selp // selectin, platelet // 1 H2.2|1 71.42 cM // 20344 /// ENSMUST000001 Selp 0.00496961 -2.44217ENSMUST00000175407 // Gm23375 // predicted gene, 23375 // --- // --- /// ENSMUST0000009 Gm23375 8.35E-05 -2.44033ENSMUST00000141741 // Gm16933 // predicted gene, 16933 // --- // --- /// AK041498 // Pl Gm16933 0.000112409 -2.43898NR_001584 // Speer8-ps1 // spermatogenesis associated glutamate (E)-rich protein 8, pse Speer8-ps1 0.00500124 -2.43793NM_018782 // Calcrl // calcitonin receptor-like // 2 D|2 // 54598 /// ENSMUST0000007426 Calcrl 1.95E-05 -2.43711NM_011809 // Ets2 // E26 avian leukemia oncogene 2, 3 domain // 16 C3-qter|16 56.64 cM Ets2 5.96E-06 -2.43676ENSMUST00000083239 // Gm22127 // predicted gene, 22127 // --- // --- Gm22127 0.00427919 -2.42909NM_011817 // Gadd45g // growth arrest and DNA-damage-inducible 45 gamma // 13|13 A5-B / Gadd45g 3.81E-06 -2.42858NM_009621 // Adamts1 // a disintegrin-like and metallopeptidase (reprolysin type) with Adamts1 0.00164919 -2.42763NM_021788 // Sap30 // sin3 associated polypeptide // 8 B2|8 29.85 cM // 60406 /// ENSMU Sap30 1.23E-06 -2.42748NM_183201 // Slfn5 // schlafen 5 // 11 C|11 // 327978 /// XR_388481 // Slfn5 // schlafe Slfn5 0.000146777 -2.42458ENSMUST00000049281 // Fam53c // family with sequence similarity 53, member C // 18 B1|1 Fam53c 0.000295537 -2.42399NM_001285959 // Lyrm1 // LYR motif containing 1 // 7 F2|7 // 73919 /// NM_001285960 // Lyrm1 0.00450329 -2.42181NM_009878 // Cdkn2d // cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4) // 9 A Cdkn2d 8.86E-05 -2.4217NM_026827 // Tmem219 // transmembrane protein 219 // 7|7 F4 // 68742 /// NM_028389 // T Tmem219 5.21E-05 -2.42085NM_013825 // Ly75 // lymphocyte antigen 75 // 2 C1.1|2 // 17076 /// ENSMUST00000028362 Ly75 0.000143763 -2.42025NM_001146176 // Max // Max protein // 12 D1-D3|12 33.78 cM // 17187 /// NM_008558 // Ma Max 2.64E-07 -2.41925NM_001014996 // Cenpj // centromere protein J // 14 C3|14 // 219103 /// ENSMUST00000065 Cenpj 0.000106316 -2.41439NM_028595 // Ms4a6c // membrane-spanning 4-domains, subfamily A, member 6C // 19 A|19 / Ms4a6c 0.000115983 -2.413--- 0.00109035 -2.4127--- 0.000154202 -2.4125NM_008146 // Golga3 // golgi autoantigen, golgin subfamily a, 3 // 5 F|5 53.36 cM // 26 Golga3 9.39E-05 -2.41198

NM_001141981 // Rbm43 // RNA binding motif protein 43 // 2|2 C1 // 71684 /// NM_0011419 Rbm43 1.29E-06 -2.41014NM_001038641 // Slx4ip // SLX4 interacting protein // 2|2 G1 // 74243 /// NM_028201 // Slx4ip 0.00500833 -2.40446NM_013642 // Dusp1 // dual specificity phosphatase 1 // 17 A2-C|17 13.28 cM // 19252 // Dusp1 5.32E-07 -2.40218NM_172815 // Rspo2 // R-spondin 2 homolog (Xenopus laevis) // 15 B3.1-B3.2|15 16.73 cM Rspo2 5.13E-05 -2.40182NM_001254946 // BC035044 // cDNA sequence BC035044 // 6 F3|6 // 232406 /// ENSMUST00000 BC035044 0.000135768 -2.40145NM_153074 // Lrrc25 // leucine rich repeat containing 25 // 8 B3.3|8 // 211228 /// ENSM Lrrc25 0.000221657 -2.40136--- 0.00506057 -2.3998--- 0.00506057 -2.3998NM_001113530 // Csf1 // colony stimulating factor 1 (macrophage) // 3 F3|3 46.83 cM // Csf1 4.50E-07 -2.39582NM_030017 // Rdh12 // retinol dehydrogenase 12 // 12|12 D2 // 77974 /// XM_006516372 // Rdh12 6.73E-05 -2.39497NR_030490 // Mir709 // microRNA 709 // 8|8 // 735271 /// ENSMUST00000102190 // Mir709 / Mir709 0.00111321 -2.39326NM_015766 // Ebi3 // Epstein-Barr virus induced gene 3 // 17 D|17 29.08 cM // 50498 /// Ebi3 0.000103225 -2.39155NM_001161770 // Lmo4 // LIM domain only 4 // 3 H2|3 68.61 cM // 16911 /// ENSMUST000001 Lmo4 3.75E-05 -2.39121--- 0.00131556 -2.39052NM_019471 // Mmp10 // matrix metallopeptidase 10 // 9 A1|9 // 17384 /// ENSMUST00000034 Mmp10 0.00176886 -2.39029NM_029362 // Chmp4b // charged multivesicular body protein 4B // 2|2 H2 // 75608 /// EN Chmp4b 3.40E-08 -2.38818NM_001045514 // Akna // AT-hook transcription factor // 4 C1|4 // 100182 /// XM_0065375 Akna 0.00154755 -2.38814ENSMUST00000055018 // Lpar1 // lysophosphatidic acid receptor 1 // 4 B3|4 32.2 cM // 14 Lpar1 0.000159378 -2.38708--- 0.00041386 -2.38616ENSMUST00000025684 // Ehd1 // EH-domain containing 1 // 19 A|19 4.4 cM // 13660 /// AK0 Ehd1 0.00502344 -2.38059ENSMUST00000113438 // Adamts9 // a disintegrin-like and metallopeptidase (reprolysin ty Adamts9 0.00245839 -2.37817ENSMUST00000091905 // Gm4950 // predicted pseudogene 4950 // --- // --- Gm4950 0.00360783 -2.37769ENSMUST00000157685 // Gm26183 // predicted gene, 26183 // --- // --- Gm26183 0.00387953 -2.37758NM_025697 // Spryd7 // SPRY domain containing 7 // 14 D1|14 // 66674 /// XM_006519394 / Spryd7 3.33E-06 -2.37345NM_178065 // Arel1 // apoptosis resistant E3 ubiquitin protein ligase 1 // 12 D2|12 // Arel1 4.63E-06 -2.37271NM_018830 // Asah2 // N-acylsphingosine amidohydrolase 2 // 19|19 C3 // 54447 /// ENSMU Asah2 0.000473136 -2.37084NR_004446 // H2-K2 // histocompatibility 2, K region locus 2 // 17 B1|17 17.98 cM // 63 H2-K2 0.00655311 -2.36984NM_010904 // Nefh // neurofilament, heavy polypeptide // 11 A1-A5|11 3.12 cM // 380684 Nefh 0.00645363 -2.36872NM_001286040 // Anks1 // ankyrin repeat and SAM domain containing 1 // 17 A3.3|17 // 22 Anks1 1.85E-05 -2.3683NM_173386 // Mb21d1 // Mab-21 domain containing 1 // 9 E1|9 // 214763 /// ENSMUST000000 Mb21d1 0.00170559 -2.36817NM_009969 // Csf2 // colony stimulating factor 2 (granulocyte-macrophage) // 11 B1.3|11 Csf2 0.000541016 -2.36396XR_379082 // LOC102639683 // uncharacterized LOC102639683 // --- // 102639683 /// ENSMU LOC102639683 0.0041535 -2.36247NM_146168 // Vopp1 // vesicular, overexpressed in cancer, prosurvival protein 1 // 6 B3 Vopp1 0.000178582 -2.36242NM_025730 // Lrrk2 // leucine-rich repeat kinase 2 // 15|15 F1 // 66725 /// XM_00652127 Lrrk2 7.71E-05 -2.36153ENSMUST00000077472 // Chst15 // carbohydrate (N-acetylgalactosamine 4-sulfate 6-O) sulf Chst15 4.41E-05 -2.36094NM_019835 // B4galt5 // UDP-Gal:betaGlcNAc beta 1,4-galactosyltransferase, polypeptide B4galt5 1.77E-06 -2.36076NM_001005740 // Phactr1 // phosphatase and actin regulator 1 // 13 A4|13 // 218194 /// Phactr1 0.000336596 -2.35827ENSMUST00000074761 // Gm10134 // predicted gene 10134 // --- // --- /// AK136568 // Gm1 Gm10134 0.002436 -2.35481ENSMUST00000181718 // Gm26750 // predicted gene, 26750 // --- // --- Gm26750 0.000511348 -2.35454XR_388923 // LOC102635154 // uncharacterized LOC102635154 // --- // 102635154 /// XR_38 LOC102635154 0.00108419 -2.35308NM_001005510 // Syne2 // spectrin repeat containing, nuclear envelope 2 // 12 C3|12 33. Syne2 0.000318676 -2.35178NM_001163686 // Dok5 // docking protein 5 // 2 H3|2 92.26 cM // 76829 /// NM_029761 // Dok5 0.00143846 -2.34849XM_006538833 // Tnfrsf14 // tumor necrosis factor receptor superfamily, member 14 (herp Tnfrsf14 3.05E-05 -2.34782NM_007961 // Etv6 // ets variant 6 // 6 G2|6 64.58 cM // 14011 /// XM_006505514 // Etv6 Etv6 1.23E-05 -2.34734NM_178592 // Abhd16a // abhydrolase domain containing 16A // 17 B1|17 18.59 cM // 19374 Abhd16a 1.44E-06 -2.34639NM_001162909 // Spaca6 // sperm acrosome associated 6 // 17 A3.2|17 // 75202 /// ENSMUS Spaca6 0.00097541 -2.34421NM_001288586 // Mdm2 // transformed mouse 3T3 cell double minute 2 // 10 C1-C3|10 66.32 Mdm2 3.51E-06 -2.34001NM_207209 // Sec24b // Sec24 related gene family, member B (S. cerevisiae) // 3 G3|3 // Sec24b 3.27E-05 -2.33746NM_001080818 // Cdc14a // CDC14 cell division cycle 14A // 3 G1|3 // 229776 /// NM_0011 Cdc14a 0.000501833 -2.33691NM_021547 // Stard3 // START domain containing 3 // 11 D|11 // 59045 /// XM_006533897 / Stard3 3.00E-06 -2.33662NM_001110209 // Lnp // limb and neural patterns // 2 C3|2 // 69605 /// NM_027133 // Lnp Lnp 3.16E-07 -2.33299--- 0.000636592 -2.33132NM_028627 // Psd // pleckstrin and Sec7 domain containing // 19 C3|19 38.8 cM // 73728 Psd 0.00150176 -2.33058--- 0.00105417 -2.32838NM_018776 // Crlf3 // cytokine receptor-like factor 3 // 11 B5|11 47.43 cM // 54394 /// Crlf3 0.000301467 -2.32813ENSMUST00000151282 // Gm11706 // predicted gene 11706 // --- // --- Gm11706 0.000672326 -2.32405--- 3.88E-05 -2.32034NM_030743 // Rnf114 // ring finger protein 114 // 2 H3|2 // 81018 /// XM_006500439 // R Rnf114 3.55E-06 -2.31856NM_001113326 // Msr1 // macrophage scavenger receptor 1 // 8 A4|8 23.89 cM // 20288 /// Msr1 3.60E-06 -2.31852ENSMUST00000079684 // Gm8394 // predicted gene 8394 // --- // --- Gm8394 1.12E-06 -2.31798NM_001008549 // Zfp658 // zinc finger protein 658 // 7 B4|7 // 210104 /// ENSMUST000001 Zfp658 0.0021967 -2.31791--- 0.00225795 -2.31784NM_001033362 // Gm614 // predicted gene 614 // X D|X // 245536 /// ENSMUST00000101358 / Gm614 8.90E-05 -2.31763NM_007553 // Bmp2 // bone morphogenetic protein 2 // 2 F2|2 65.21 cM // 12156 /// ENSMU Bmp2 0.000119543 -2.31558NM_146122 // Dennd1a // DENN/MADD domain containing 1A // 2 B|2 // 227801 /// ENSMUST00 Dennd1a 8.77E-05 -2.3146NM_010724 // Psmb8 // proteasome (prosome, macropain) subunit, beta type 8 (large multi Psmb8 1.39E-06 -2.31414NM_010361 // Gstt2 // glutathione S-transferase, theta 2 // 10 B5-C1|10 38.58 cM // 148 Gstt2 0.00145952 -2.31344NM_001081105 // Rhoh // ras homolog gene family, member H // 5|5 D // 74734 /// ENSMUST Rhoh 0.000604671 -2.31303NM_029077 // Trim14 // tripartite motif-containing 14 // 4|4 B2 // 74735 /// ENSMUST000 Trim14 8.68E-06 -2.30868NM_026386 // Snx2 // sorting nexin 2 // 18 D1|18 // 67804 /// ENSMUST00000037850 // Snx Snx2 1.11E-05 -2.30859--- 0.00616137 -2.30841XM_006499876 // Shf // Src homology 2 domain containing F // 2 E5|2 // 435684 /// NM_00 Shf 0.00029808 -2.30765NM_001142952 // Fam46c // family with sequence similarity 46, member C // 3 F2.2|3 // 7 Fam46c 0.000145702 -2.30754NM_008211 // H3f3b // H3 histone, family 3B // 11 E2|11 // 15081 /// XM_006532248 // H3 H3f3b 2.15E-05 -2.30571NM_010945 // Nsmaf // neutral sphingomyelinase (N-SMase) activation associated factor / Nsmaf 4.95E-06 -2.30441NM_021397 // Zbtb32 // zinc finger and BTB domain containing 32 // 7 B2-B3|7 // 58206 / Zbtb32 0.000771819 -2.30333XR_378383 // LOC102638993 // uncharacterized LOC102638993 // --- // 102638993 /// XR_37 LOC102638993 0.00526386 -2.30311NM_001201460 // H2-Q9 // histocompatibility 2, Q region locus 9 // 17|17 // 110558 /// H2-Q9 3.76E-05 -2.30262NM_001159633 // Slc44a1 // solute carrier family 44, member 1 // 4 B2|4 // 100434 /// N Slc44a1 3.20E-06 -2.30246NM_011074 // Cdk14 // cyclin-dependent kinase 14 // 5 A1|5 2.61 cM // 18647 /// XM_0065 Cdk14 0.000429088 -2.30197NM_010851 // Myd88 // myeloid differentiation primary response gene 88 // 9 F3|9 71.33 Myd88 0.00010043 -2.30181NM_001024716 // Triobp // TRIO and F-actin binding protein // 15 E1|15 37.7 cM // 11025 Triobp 2.12E-05 -2.30156NR_003363 // Gm6548 // eukaryotic translation elongation factor 1 alpha 1 pseudogene // Gm6548 2.85E-05 -2.30111--- 0.000963336 -2.30072NM_172831 // E230025N22Rik // Riken cDNA E230025N22 gene // 18 B2|18 // 240216 /// XM_0 E230025N22Rik 0.00588126 -2.29493NM_007808 // Cycs // cytochrome c, somatic // 6 B2.3|6 24.32 cM // 13063 /// ENSMUST000 Cycs 9.31E-05 -2.28999NM_001008233 // Plekhn1 // pleckstrin homology domain containing, family N member 1 // Plekhn1 0.000130854 -2.28824ENSMUST00000174699 // H2-Q6 // histocompatibility 2, Q region locus 6 // 17 B1|17 18.66 H2-Q6 5.83E-05 -2.28775--- 0.00047417 -2.287NM_011627 // Tpbg // trophoblast glycoprotein // 9 E3.1|9 // 21983 /// ENSMUST000000065 Tpbg 1.19E-05 -2.28391NM_001253804 // Slc12a4 // solute carrier family 12, member 4 // 8 D3|8 53.06 cM // 204 Slc12a4 7.46E-05 -2.28081NM_001146318 // Cnp // 2,3-cyclic nucleotide 3 phosphodiesterase // 11 D|11 63.47 cM // Cnp 0.000102373 -2.2788NM_145447 // Mfsd7c // major facilitator superfamily domain containing 7C // 12 D2|12 / Mfsd7c 0.000138417 -2.27326

ENSMUST00000132017 // Vps54 // vacuolar protein sorting 54 (yeast) // 11 A3|11 13.89 cM Vps54 2.20E-05 -2.27251NM_010757 // Mafk // v-maf musculoaponeurotic fibrosarcoma oncogene family, protein K ( Mafk 9.32E-06 -2.27247NM_172894 // Ppp6r1 // protein phosphatase 6, regulatory subunit 1 // 7 A1|7 // 243819 Ppp6r1 1.84E-07 -2.27202NM_198865 // Slitrk5 // SLIT and NTRK-like family, member 5 // 14|14 E3 // 75409 /// XM Slitrk5 0.00341687 -2.27197NM_001145979 // Gtpbp2 // GTP binding protein 2 // 17|17 C-D // 56055 /// NM_019581 // Gtpbp2 6.53E-06 -2.27145NM_011916 // Xrn1 // 5-3 exoribonuclease 1 // 9|9 E4 // 24127 /// ENSMUST00000034981 // Xrn1 7.77E-06 -2.27023NM_001276764 // Dst // dystonin // 1 B|1 12.91 cM // 13518 /// NM_010081 // Dst // dyst Dst 0.00271654 -2.27001NM_138953 // Ell2 // elongation factor RNA polymerase II 2 // 13 C1|13 // 192657 /// EN Ell2 0.000231616 -2.26996NM_153402 // Ago3 // argonaute RISC catalytic subunit 3 // 4 D2.2|4 // 214150 /// XM_00 Ago3 0.000315432 -2.26807NM_009763 // Bst1 // bone marrow stromal cell antigen 1 // 5 B3|5 23.84 cM // 12182 /// Bst1 4.95E-06 -2.26591ENSMUST00000139214 // 4930430E12Rik // RIKEN cDNA 4930430E12 gene // --- // --- /// ENS 4930430E12Rik 5.40E-06 -2.26513XM_006538385 // Gm11787 // predicted gene 11787 // 4 A1|4 // 666513 /// ENSMUST00000121 Gm11787 0.00026155 -2.26456NM_027498 // Sik3 // SIK family kinase 3 // 9 A5.2|9 // 70661 /// ENSMUST00000120247 // Sik3 4.74E-05 -2.26437NM_145977 // Slc45a3 // solute carrier family 45, member 3 // 1 E4|1 // 212980 /// ENSM Slc45a3 0.000170437 -2.26018NM_008846 // Pip5k1b // phosphatidylinositol-4-phosphate 5-kinase, type 1 beta // 19|19 Pip5k1b 0.00515638 -2.25943NM_007483 // Rhob // ras homolog gene family, member B // 12 A1.1|12 // 11852 /// ENSMU Rhob 5.19E-06 -2.25859NM_009943 // Cox6a2 // cytochrome c oxidase subunit VIa polypeptide 2 // 7 F3|7 70.04 c Cox6a2 0.000985748 -2.25662NR_035410 // Mir669k // microRNA 669k // 2|2 8.22 cM // 100316663 /// ENSMUST0000017774 Mir669k 0.00073378 -2.2529ENSMUST00000102715 // Stk39 // serine/threonine kinase 39 // 2|2 C3 // 53416 /// BC0519 Stk39 0.00332107 -2.25195NM_009910 // Cxcr3 // chemokine (C-X-C motif) receptor 3 // X D|X 44.58 cM // 12766 /// Cxcr3 0.000840818 -2.24895NM_011803 // Klf6 // Kruppel-like factor 6 // 13 A1|13 // 23849 /// ENSMUST00000000080 Klf6 8.13E-07 -2.24873NR_033552 // Gm10125 // predicted gene 10125 // --- // 791318 /// ENSMUST00000161096 // Gm10125 0.00447638 -2.248--- 0.00682687 -2.24559--- 0.00682687 -2.24559ENSMUST00000157305 // Gm26048 // predicted gene, 26048 // --- // --- Gm26048 0.00115545 -2.24405NM_145931 // Zc3h7a // zinc finger CCCH type containing 7 A // 16 A1|16 // 106205 /// N Zc3h7a 6.58E-06 -2.23798ENSMUST00000140556 // Gm11206 // predicted gene 11206 // --- // --- /// AK053136 // Ada Gm11206 3.59E-05 -2.2371NM_028850 // Chic2 // cysteine-rich hydrophobic domain 2 // 5|5 D // 74277 /// ENSMUST0 Chic2 8.12E-09 -2.23453NM_198642 // 5031414D18Rik // RIKEN cDNA 5031414D18 gene // 14 D3|14 // 271221 /// ENSM 5031414D18Rik 0.000537487 -2.22932NM_008343 // Igfbp3 // insulin-like growth factor binding protein 3 // 11 A1|11 4.75 cM Igfbp3 0.00618744 -2.22845NM_007825 // Cyp7b1 // cytochrome P450, family 7, subfamily b, polypeptide 1 // 3 A1|3 Cyp7b1 0.000393202 -2.22807NM_022028 // Sav1 // salvador homolog 1 (Drosophila) // 12|12 C3 // 64010 /// ENSMUST00 Sav1 4.47E-06 -2.22533NM_026405 // Rab32 // RAB32, member RAS oncogene family // 10 A1|10 // 67844 /// ENSMUS Rab32 1.35E-05 -2.22218NM_018807 // Plagl2 // pleiomorphic adenoma gene-like 2 // 2|2 H2 // 54711 /// ENSMUST0 Plagl2 1.84E-05 -2.22067NM_028283 // Uaca // uveal autoantigen with coiled-coil domains and ankyrin repeats // Uaca 2.65E-05 -2.21961NM_029749 // Usp42 // ubiquitin specific peptidase 42 // 5 G2|5 82.5 cM // 76800 /// XM Usp42 1.53E-06 -2.21851NM_023731 // Ccdc86 // coiled-coil domain containing 86 // 19 B|19 7.41 cM // 108673 // Ccdc86 0.000752336 -2.21489XM_006497832 // Psd4 // pleckstrin and Sec7 domain containing 4 // 2 A3|2 // 215632 /// Psd4 0.000201774 -2.21377--- 0.00254822 -2.21364NM_001170855 // Trim36 // tripartite motif-containing 36 // 18 C|18 24.41 cM // 28105 / Trim36 0.00495473 -2.21311ENSMUST00000119109 // Etv3 // ets variant 3 // 3 F1|3 // 27049 /// NM_001083318 // Etv3 Etv3 6.82E-06 -2.21093XM_006529693 // A630001G21Rik // RIKEN cDNA A630001G21 gene // 1 C5|1 // 319997 /// XM_ A630001G21Rik 0.000182763 -2.20868NM_001126047 // Sema4c // sema domain, immunoglobulin domain (Ig), transmembrane domain Sema4c 0.0010019 -2.20786NM_152804 // Plk2 // polo-like kinase 2 // 13|13 D2.1 // 20620 /// ENSMUST00000022212 / Plk2 3.04E-06 -2.20744NM_145373 // Sectm1a // secreted and transmembrane 1A // 11 E2|11 // 209588 /// XM_0065 Sectm1a 0.00029203 -2.20666NM_001177785 // Cd44 // CD44 antigen // 2 E2|2 54.13 cM // 12505 /// NM_009851 // Cd44 Cd44 1.44E-06 -2.20084NM_033541 // Oas1c // 2-5 oligoadenylate synthetase 1C // 5 F|5 60.64 cM // 114643 /// Oas1c 4.07E-05 -2.19879NM_030705 // Mesdc1 // mesoderm development candidate 1 // 7 D3|7 // 80889 /// ENSMUST0 Mesdc1 0.000476074 -2.19709ENSMUST00000145372 // Gm15347 // predicted gene 15347 // --- // --- Gm15347 0.000274216 -2.19655NM_028791 // Cmtr1 // cap methyltransferase 1 // 17 A3.3|17 // 74157 /// ENSMUST0000002 Cmtr1 9.09E-06 -2.19537NM_144880 // Ppp2r5a // protein phosphatase 2, regulatory subunit B, alpha // 1 H6|1 // Ppp2r5a 1.06E-05 -2.19405ENSMUST00000107254 // Rfx5 // regulatory factor X, 5 (influences HLA class II expressio Rfx5 3.31E-05 -2.19392--- 0.00309587 -2.19264NM_001083810 // Prr5l // proline rich 5 like // 2 E2|2 // 72446 /// NM_001110849 // Prr Prr5l 0.000752878 -2.19138ENSMUST00000163078 // Ms4a6b // membrane-spanning 4-domains, subfamily A, member 6B // Ms4a6b 1.12E-05 -2.19091NM_172133 // Adap2 // ArfGAP with dual PH domains 2 // 11 B5|11 47.56 cM // 216991 /// Adap2 7.77E-06 -2.18916NM_008506 // Mycl // v-myc myelocytomatosis viral oncogene homolog, lung carcinoma deri Mycl 0.00528039 -2.18821--- 0.000421869 -2.18782NM_016696 // Gpc1 // glypican 1 // 1 D|1 // 14733 /// XM_006529142 // Gpc1 // glypican Gpc1 0.000107371 -2.18762ENSMUST00000104261 // Gm23127 // predicted gene, 23127 // --- // --- /// AK163470 // El Gm23127 0.00112951 -2.18624ENSMUST00000166606 // Gm17092 // predicted gene 17092 // --- // --- Gm17092 0.00320153 -2.18548NM_001284503 // Cask // calcium/calmodulin-dependent serine protein kinase (MAGUK famil Cask 0.000291833 -2.18494NM_145501 // Pi4k2a // phosphatidylinositol 4-kinase type 2 alpha // 19 C3|19 35.74 cM Pi4k2a 2.16E-05 -2.18237ENSMUST00000122797 // Gm25292 // predicted gene, 25292 // --- // --- Gm25292 0.000450445 -2.18055NM_001039530 // Parp14 // poly (ADP-ribose) polymerase family, member 14 // 16 B3|16 // Parp14 0.00236812 -2.18022ENSMUST00000033900 // Rab20 // RAB20, member RAS oncogene family // 8 A1.1|8 5.73 cM // Rab20 0.000159645 -2.17983NR_029539 // Mir125a // microRNA 125a // 17|17 // 387235 /// ENSMUST00000083545 // Mir1 Mir125a 0.00229509 -2.17776AK084985 // Gm10099 // predicted gene 10099 // --- // 791367 Gm10099 0.00430591 -2.1771ENSMUST00000032429 // Med21 // mediator complex subunit 21 // 6 G3|6 77.7 cM // 108098 Med21 0.000266945 -2.17671XM_006498189 // Pdss1 // prenyl (solanesyl) diphosphate synthase, subunit 1 // 2 A3|2 / Pdss1 0.00440768 -2.17654--- 0.000129226 -2.17566NM_001159318 // Il1rap // interleukin 1 receptor accessory protein // 16|16 B2 // 16180 Il1rap 0.00160796 -2.17541NM_001139520 // Samhd1 // SAM domain and HD domain, 1 // 2|2 H2 // 56045 /// NM_018851 Samhd1 0.00016474 -2.17431--- 5.00E-05 -2.17363NM_008247 // Ppap2a // phosphatidic acid phosphatase type 2A // 13 D2.2|13 // 19012 /// Ppap2a 0.000125752 -2.17352NM_001289593 // Kynu // kynureninase (L-kynurenine hydrolase) // 2|2 C1 // 70789 /// NM Kynu 6.89E-05 -2.17075NM_001033535 // Tnfaip8l3 // tumor necrosis factor, alpha-induced protein 8-like 3 // 9 Tnfaip8l3 0.00229495 -2.17021NM_175136 // Rnf122 // ring finger protein 122 // 8 A3|8 // 68867 /// XM_006509189 // R Rnf122 0.00106681 -2.16985--- 0.00211133 -2.16874NM_001081175 // Itpkb // inositol 1,4,5-trisphosphate 3-kinase B // 1 H5|1 84.27 cM // Itpkb 2.79E-06 -2.16793NM_025541 // Asf1a // anti-silencing function 1A histone chaperone // 10 B3|10 // 66403 Asf1a 5.84E-05 -2.16711NM_010799 // Minpp1 // multiple inositol polyphosphate histidine phosphatase 1 // 19 C1 Minpp1 1.04E-05 -2.16551NM_133857 // Usp53 // ubiquitin specific peptidase 53 // 3|3 G3 // 99526 /// ENSMUST000 Usp53 0.000235766 -2.16506--- 0.000543646 -2.16394--- 0.00516157 -2.16068NM_013822 // Jag1 // jagged 1 // 2 F3|2 67.73 cM // 16449 /// ENSMUST00000028735 // Jag Jag1 5.46E-05 -2.16041NM_133838 // Ehd4 // EH-domain containing 4 // 2 E5|2 // 98878 /// ENSMUST00000028755 / Ehd4 0.000135581 -2.1601NM_001040400 // Tet2 // tet methylcytosine dioxygenase 2 // 3 G3|3 // 214133 /// ENSMUS Tet2 2.10E-05 -2.15969NM_007395 // Acvr1b // activin A receptor, type 1B // 15 F2|15 56.48 cM // 11479 /// XM Acvr1b 0.00456837 -2.15669NM_001114664 // Iqsec2 // IQ motif and Sec7 domain 2 // X F3|X 68.46 cM // 245666 /// E Iqsec2 0.000105667 -2.15653--- 0.000534393 -2.15232--- 0.00135901 -2.15142NM_019577 // Ccl24 // chemokine (C-C motif) ligand 24 // 5|5 G1 // 56221 /// XM_0065044 Ccl24 0.00276187 -2.15067

NM_021525 // Rcl1 // RNA terminal phosphate cyclase-like 1 // 19 C1|19 // 59028 /// ENS Rcl1 0.000137546 -2.15035ENSMUST00000179566 // Gm6132 // predicted pseudogene 6132 // --- // --- Gm6132 0.00579678 -2.14802BC003781 // Ube2e1 // ubiquitin-conjugating enzyme E2E 1 // 14|14 A3 // 22194 /// NM_00 Ube2e1 0.000191353 -2.14627NM_001164357 // Slc25a25 // solute carrier family 25 (mitochondrial carrier, phosphate Slc25a25 0.00681602 -2.14592NM_001081269 // Whsc1l1 // Wolf-Hirschhorn syndrome candidate 1-like 1 (human) // 8 A2| Whsc1l1 7.92E-06 -2.1437NM_026205 // Rnf151 // ring finger protein 151 // 17 A3.3|17 // 67504 /// ENSMUST000000 Rnf151 0.002558 -2.14315ENSMUST00000169859 // Gm17542 // predicted gene, 17542 // --- // --- Gm17542 0.000676133 -2.14269NM_009192 // Sla // src-like adaptor // 15 D2|15 29.3 cM // 20491 /// ENSMUST0000010057 Sla 0.000434109 -2.14055--- 0.00139158 -2.13904NM_001160251 // Zfp281 // zinc finger protein 281 // 1 E4|1 // 226442 /// NM_177643 // Zfp281 2.82E-05 -2.13708NM_001195632 // Arhgap32 // Rho GTPase activating protein 32 // 9 A4|9 // 330914 /// XM Arhgap32 0.00441146 -2.13327ENSMUST00000149688 // Mthfs // 5, 10-methenyltetrahydrofolate synthetase // 9 E3.1|9 // Mthfs 0.000462576 -2.1331NM_011464 // Spint2 // serine protease inhibitor, Kunitz type 2 // 7 B1|7 // 20733 /// Spint2 0.00160529 -2.13227NM_133224 // Atp13a1 // ATPase type 13A1 // 8 B3.3|8 // 170759 /// XM_006509564 // Atp1 Atp13a1 5.90E-07 -2.1255--- 0.000802589 -2.12403NM_001039103 // Rasa4 // RAS p21 protein activator 4 // 5 G2|5 // 54153 /// NM_133914 / Rasa4 8.52E-05 -2.12392NM_001081127 // Adamts14 // a disintegrin-like and metallopeptidase (reprolysin type) w Adamts14 0.00258158 -2.12334NM_001130409 // Ptk2 // PTK2 protein tyrosine kinase 2 // 15 D3|15 33.94 cM // 14083 // Ptk2 1.20E-05 -2.12326NM_010637 // Klf4 // Kruppel-like factor 4 (gut) // 4 B3|4 29.76 cM // 16600 /// ENSMUS Klf4 0.00371537 -2.12325NM_133661 // Slc6a12 // solute carrier family 6 (neurotransmitter transporter, betaine/ Slc6a12 0.0011636 -2.12259NM_001162465 // Dtnb // dystrobrevin, beta // 12 A1.1|12 1.88 cM // 13528 /// NM_007886 Dtnb 0.00395701 -2.12053NM_198861 // Lrrc75a // leucine rich repeat containing 75A // 11 B2|11 // 192976 /// XM Lrrc75a 1.14E-05 -2.11958NM_198647 // Tbc1d22b // TBC1 domain family, member 22B // 17 A3.3|17 // 381085 /// ENS Tbc1d22b 0.000102711 -2.11876NM_001163014 // Gp6 // glycoprotein 6 (platelet) // 7 A1|7 // 243816 /// XM_006539909 / Gp6 0.00465879 -2.11699NM_001033310 // Cox18 // cytochrome c oxidase assembly protein 18 // 5 E1|5 // 231430 / Cox18 2.90E-05 -2.11666NM_011030 // P4ha1 // procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydr P4ha1 2.04E-05 -2.11498NM_007764 // Crkl // v-crk sarcoma virus CT10 oncogene homolog (avian)-like // 16 A3|16 Crkl 1.32E-05 -2.11471--- 0.000905674 -2.11464NM_033524 // Spred1 // sprouty protein with EVH-1 domain 1, related sequence // 2 E5|2 Spred1 8.36E-05 -2.11319NM_001159750 // Tcea1 // transcription elongation factor A (SII) 1 // 1 A1|1 // 21399 / Tcea1 6.63E-05 -2.11152NM_080575 // Acss1 // acyl-CoA synthetase short-chain family member 1 // 2 G3|2 // 6873 Acss1 3.55E-05 -2.11147NM_011669 // Usp12 // ubiquitin specific peptidase 12 // 5|5 G2 // 22217 /// ENSMUST000 Usp12 0.000122171 -2.10955NM_008136 // Gnl1 // guanine nucleotide binding protein-like 1 // 17 C-D|17 18.82 cM // Gnl1 0.000240002 -2.1091NM_001290504 // Mid1 // midline 1 // X and Y|X 79.19 cM // 17318 /// NM_001290505 // Mi Mid1 0.000190971 -2.10712NM_009807 // Casp1 // caspase 1 // 9 A1|9 2.46 cM // 12362 /// ENSMUST00000027015 // Ca Casp1 0.000574646 -2.10687NM_001005605 // Aebp2 // AE binding protein 2 // 6|6 G1 // 11569 /// NM_178803 // Aebp2 Aebp2 1.06E-05 -2.10664NM_145834 // Il17c // interleukin 17C // 8 E1|8 // 234836 /// ENSMUST00000050963 // Il1 Il17c 0.00521711 -2.10369NM_001003909 // Ankib1 // ankyrin repeat and IBR domain containing 1 // 5 A1|5 // 70797 Ankib1 1.37E-06 -2.10172NM_001081194 // Kcnh4 // potassium voltage-gated channel, subfamily H (eag-related), me Kcnh4 0.00684467 -2.10076NM_001163283 // Zbtb5 // zinc finger and BTB domain containing 5 // 4 B1|4 // 230119 // Zbtb5 0.000926799 -2.10035NM_019788 // Bloc1s6 // biogenesis of lysosomal organelles complex-1, subunit 6, pallid Bloc1s6 2.83E-05 -2.09963ENSMUST00000052876 // Eva1b // eva-1 homolog B (C. elegans) // 4 D2.2|4 // 230752 /// N Eva1b 3.48E-05 -2.0994NM_007808 // Cycs // cytochrome c, somatic // 6 B2.3|6 24.32 cM // 13063 /// ENSMUST000 Cycs 0.000658662 -2.09485NM_001164671 // Dnaja1 // DnaJ (Hsp40) homolog, subfamily A, member 1 // 4 A5|4 // 1550 Dnaja1 2.06E-06 -2.09462NM_144943 // Cd207 // CD207 antigen // 6|6 D1-D2 // 246278 /// ENSMUST00000037882 // Cd Cd207 0.00106586 -2.09373NM_133757 // Pgs1 // phosphatidylglycerophosphate synthase 1 // 11 E2|11 // 74451 /// X Pgs1 0.000125692 -2.09251NM_001127177 // Ptpn2 // protein tyrosine phosphatase, non-receptor type 2 // 18 E1|18 Ptpn2 0.000808082 -2.09185NM_001079824 // Hnrnph3 // heterogeneous nuclear ribonucleoprotein H3 // 10 B4|10 // 43 Hnrnph3 0.000110272 -2.09177NM_022018 // Fam129a // family with sequence similarity 129, member A // 1 G2|1 // 6391 Fam129a 9.96E-06 -2.09168ENSMUST00000118518 // Gm12003 // predicted gene 12003 // --- // --- /// ENSMUST00000175 Gm12003 7.30E-05 -2.09135AK191337 // Fam53c // family with sequence similarity 53, member C // 18 B1|18 // 66306 Fam53c 0.00208074 -2.09127NM_001162941 // Mapre2 // microtubule-associated protein, RP/EB family, member 2 // 18 Mapre2 0.000263543 -2.08959NM_009323 // Tbx15 // T-box 15 // 3 F2.2|3 43.03 cM // 21384 /// ENSMUST00000029462 // Tbx15 0.000964077 -2.08858NM_008689 // Nfkb1 // nuclear factor of kappa light polypeptide gene enhancer in B cell Nfkb1 0.000780274 -2.08672NM_010499 // Ier2 // immediate early response 2 // 8 C3|8 41.02 cM // 15936 /// ENSMUST Ier2 5.70E-06 -2.08637NM_019868 // Hnrnph2 // heterogeneous nuclear ribonucleoprotein H2 // X E3|X 56.2 cM // Hnrnph2 0.00271606 -2.08347NM_025480 // Tmem128 // transmembrane protein 128 // 5 B3|5 // 66309 /// XM_006504046 / Tmem128 6.27E-05 -2.08315--- 0.00261059 -2.08235NM_001081343 // 3110043O21Rik // RIKEN cDNA 3110043O21 gene // 4 A5|4 // 73205 /// XM_0 3110043O21Rik 4.19E-05 -2.08141--- 0.000134091 -2.08064NM_001252662 // Dmtn // dematin actin binding protein // 14 D2|14 36.32 cM // 13829 /// Dmtn 4.84E-05 -2.08052NM_001080798 // Aff1 // AF4/FMR2 family, member 1 // 5 E|5 50.45 cM // 17355 /// NM_133 Aff1 3.02E-05 -2.07858NM_008587 // Mertk // c-mer proto-oncogene tyrosine kinase // 2 F1|2 // 17289 /// ENSMU Mertk 2.50E-06 -2.07811NM_001111279 // Wdfy1 // WD repeat and FYVE domain containing 1 // 1|1 C4 // 69368 /// Wdfy1 0.00373735 -2.07641NM_015800 // Crim1 // cysteine rich transmembrane BMP regulator 1 (chordin like) // 17 Crim1 0.000240154 -2.07609NM_029532 // Snrnp35 // small nuclear ribonucleoprotein 35 (U11/U12) // 5 F|5 // 76167 Snrnp35 0.000408912 -2.07537NM_001205043 // Jarid2 // jumonji, AT rich interactive domain 2 // 13 A5|13 21.66 cM // Jarid2 0.000414231 -2.07485NM_001122594 // Phlpp2 // PH domain and leucine rich repeat protein phosphatase 2 // 8 Phlpp2 1.45E-05 -2.07237ENSMUST00000150702 // Gm16292 // predicted gene 16292 // --- // --- Gm16292 0.000775688 -2.07095XR_106394 // A430060F13Rik // RIKEN cDNA A430060F13 gene // 11 D|11 // 100039739 /// XR A430060F13Rik 0.00526677 -2.07025NM_146252 // Tbc1d13 // TBC1 domain family, member 13 // 2 B|2 // 70296 /// XM_00649832 Tbc1d13 1.58E-05 -2.06952NM_172630 // Mppe1 // metallophosphoesterase 1 // 18 E1|18 // 225651 /// XM_006525888 / Mppe1 6.39E-05 -2.06675NR_039585 // Mir5124a // microRNA 5124a // 13|13 20.13 cM // 100628630 /// ENSMUST00000 Mir5124a 0.000891131 -2.06488NM_009887 // Cer1 // cerberus 1 homolog (Xenopus laevis) // 4 C3|4 39.4 cM // 12622 /// Cer1 0.00157387 -2.06486NM_008549 // Man2a1 // mannosidase 2, alpha 1 // 17|17 E1.2 // 17158 /// ENSMUST0000008 Man2a1 1.92E-06 -2.06427ENSMUST00000104327 // Gm25878 // predicted gene, 25878 // --- // --- /// ENSMUST0000013 Gm25878 0.00179752 -2.06392NM_024436 // Rab22a // RAB22A, member RAS oncogene family // 2 H4|2 97.26 cM // 19334 / Rab22a 4.47E-06 -2.06323NM_026968 // Manbal // mannosidase, beta A, lysosomal-like // 2 H1|2 // 69161 /// ENSMU Manbal 2.87E-05 -2.06197NR_040374 // A230028O05Rik // RIKEN cDNA A230028O05 gene // 16 B1|16 // 319487 /// ENSM A230028O05Rik 0.000395331 -2.06173NM_198006 // Coa5 // cytochrome C oxidase assembly factor 5 // 1 B|1 // 76178 /// ENSMU Coa5 2.45E-06 -2.06129--- 0.00356456 -2.06066NM_001167879 // Gareml // GRB2 associated, regulator of MAPK1-like // 5 B1|5 // 242915 Gareml 3.54E-05 -2.06014NM_007986 // Fap // fibroblast activation protein // 2 C1.3|2 35.85 cM // 14089 /// XM_ Fap 0.00446644 -2.05958NM_001163567 // Fam102b // family with sequence similarity 102, member B // 3 F3|3 // 3 Fam102b 9.44E-07 -2.05929XM_006530302 // Trafd1 // TRAF type zinc finger domain containing 1 // 5 F|5 // 231712 Trafd1 2.54E-07 -2.05918NM_153159 // Zc3h12a // zinc finger CCCH type containing 12A // 4 D2.2|4 // 230738 /// Zc3h12a 0.000325035 -2.05646NM_134063 // Fam208b // family with sequence similarity 208, member B // 13 A1|13 // 10 Fam208b 8.49E-06 -2.0546NM_001025438 // Camk2d // calcium/calmodulin-dependent protein kinase II, delta // 3 G1 Camk2d 0.000424678 -2.05312NM_001163703 // Dcun1d3 // DCN1, defective in cullin neddylation 1, domain containing 3 Dcun1d3 0.00450964 -2.05231NM_001146268 // Pdgfrb // platelet derived growth factor receptor, beta polypeptide // Pdgfrb 4.11E-06 -2.04805NM_023670 // Igf2bp3 // insulin-like growth factor 2 mRNA binding protein 3 // 6 B2.3|6 Igf2bp3 0.00207322 -2.04788--- 0.00180068 -2.04688NM_027642 // Phf6 // PHD finger protein 6 // X|X A4 // 70998 /// ENSMUST00000078944 // Phf6 1.31E-05 -2.04348

ENSMUST00000070283 // Dennd1b // DENN/MADD domain containing 1B // 1 F|1 // 329260 /// Dennd1b 0.000392025 -2.0412--- 0.000143293 -2.03976ENSMUST00000146121 // Gm11292 // predicted gene 11292 // 13 A3.1|13 // 193453 /// AK042 Gm11292 0.000922778 -2.03808AK157419 // Gm20100 // predicted gene, 20100 // 8|8 5.73 cM // 100504175 Gm20100 0.00276853 -2.03767NM_001005507 // Smg7 // Smg-7 homolog, nonsense mediated mRNA decay factor (C. elegans) Smg7 9.80E-06 -2.03719NM_144920 // Plekha5 // pleckstrin homology domain containing, family A member 5 // 6 G Plekha5 0.00012912 -2.03691NM_001293772 // Palld // palladin, cytoskeletal associated protein // 8|8 B3.3 // 72333 Palld 0.00139209 -2.03517NM_139311 // Mllt6 // myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Dr Mllt6 0.00354713 -2.03497NM_008029 // Flt4 // FMS-like tyrosine kinase 4 // 11 A5-B1|11 29.69 cM // 14257 /// EN Flt4 0.00237047 -2.03416NM_001168277 // Jazf1 // JAZF zinc finger 1 // 6 B3|6 25.74 cM // 231986 /// NM_173406 Jazf1 0.00384643 -2.03077--- 0.000449525 -2.02765--- 0.00409317 -2.02594NM_178607 // Rnf24 // ring finger protein 24 // 2 F1|2 63.32 cM // 51902 /// ENSMUST000 Rnf24 0.00598674 -2.02382--- 0.0006979 -2.02161NM_001113330 // Crx // cone-rod homeobox // 7 A2|7 8.6 cM // 12951 /// NM_007770 // Crx Crx 6.35E-05 -2.02048NM_011669 // Usp12 // ubiquitin specific peptidase 12 // 5|5 G2 // 22217 /// ENSMUST000 Usp12 1.31E-05 -2.01967NM_027715 // Otud1 // OTU domain containing 1 // 2 A3|2 // 71198 /// ENSMUST00000052168 Otud1 0.000403725 -2.01494ENSMUST00000038287 // Dusp5 // dual specificity phosphatase 5 // 19 D2|19 // 240672 /// Dusp5 5.20E-05 -2.0115NM_001290413 // Traf2 // TNF receptor-associated factor 2 // 2 A3|2 // 22030 /// NM_009 Traf2 0.000106918 -2.00875NM_178920 // Mal2 // mal, T cell differentiation protein 2 // 15 D1|15 // 105853 /// EN Mal2 0.000244146 -2.00869--- 0.000100489 -2.00782NM_001033439 // Lrch1 // leucine-rich repeats and calponin homology (CH) domain contain Lrch1 1.09E-08 -2.00762--- 0.00223445 -2.00684XR_381025 // LOC102639588 // uncharacterized LOC102639588 // --- // 102639588 /// ENSMU LOC102639588 0.00464431 -2.00605--- 0.000299129 -2.00356ENSMUST00000114996 // Optn // optineurin // 2 A1|2 3.15 cM // 71648 /// NM_181848 // Op Optn 2.21E-05 -2.00287NM_133190 // Cacng8 // calcium channel, voltage-dependent, gamma subunit 8 // 7 A1|7 1. Cacng8 0.0037822 -2.00287NM_009696 // Apoe // apolipoprotein E // 7 A3|7 9.94 cM // 11816 /// ENSMUST00000174064 Apoe 9.71E-07 2.00001ENSMUST00000141023 // Gm13609 // predicted gene 13609 // --- // --- /// XR_399674 // LO Gm13609 0.00606043 2.00033BC060304 // Hist1h2bg // histone cluster 1, H2bg // 13 A2-A3|13 // 319181 Hist1h2bg 0.000689603 2.00166NM_001253897 // Ecsit // ECSIT homolog (Drosophila) // 9|9 A4 // 26940 /// NM_001253898 Ecsit 0.000337805 2.00207NM_001289458 // Hgf // hepatocyte growth factor // 5 A2-A3|5 7.07 cM // 15234 /// NM_00 Hgf 0.000157874 2.00282NM_001166635 // Mid1ip1 // Mid1 interacting protein 1 (gastrulation specific G12-like ( Mid1ip1 0.000520363 2.00295NM_134255 // Elovl5 // ELOVL family member 5, elongation of long chain fatty acids (yea Elovl5 6.96E-06 2.00326--- 0.000669431 2.00349NM_001167691 // Sirt4 // sirtuin 4 // 5 F|5 // 75387 /// NM_133760 // Sirt4 // sirtuin Sirt4 5.88E-05 2.00433NM_026536 // Atp5s // ATP synthase, H+ transporting, mitochondrial F0 complex, subunit Atp5s 0.00314245 2.00453NM_007444 // Amd2 // S-adenosylmethionine decarboxylase 2 // 10 B1|10 // 100041585 /// Amd2 2.30E-05 2.00454NM_205820 // Tlr13 // toll-like receptor 13 // X D|X // 279572 /// ENSMUST00000040065 / Tlr13 2.90E-06 2.00486NM_172988 // Fbxl4 // F-box and leucine-rich repeat protein 4 // 4 A3|4 // 269514 /// N Fbxl4 0.000111174 2.00606NM_019747 // Zfp113 // zinc finger protein 113 // 5|5 G1 // 56314 /// ENSMUST0000004939 Zfp113 0.00237314 2.0068--- 0.000762576 2.00777NM_001204906 // Recql // RecQ protein-like // 6 G2|6 73.91 cM // 19691 /// NM_001204907 Recql 7.75E-06 2.00807NM_026602 // Bcas2 // breast carcinoma amplified sequence 2 // 3 F2.2|3 // 68183 /// XM Bcas2 8.03E-07 2.00843ENSMUST00000032967 // Lipt2 // lipoyl(octanoyl) transferase 2 (putative) // 7|7 F1 // 6 Lipt2 0.00259266 2.00916--- 0.00414934 2.00925NM_145398 // Casd1 // CAS1 domain containing 1 // 6 A1|6 1.81 cM // 213819 /// XM_00650 Casd1 2.43E-05 2.01072NM_001033145 // 1190002N15Rik // RIKEN cDNA 1190002N15 gene // 9 E3.3|9 // 68861 /// EN 1190002N15Rik 0.000155497 2.01109XM_006511619 // Mapkapk3 // mitogen-activated protein kinase-activated protein kinase 3 Mapkapk3 7.72E-05 2.01148NM_007924 // Ell // elongation factor RNA polymerase II // 8 C1|8 // 13716 /// ENSMUST0 Ell 0.000366188 2.01176NM_009706 // Arhgap5 // Rho GTPase activating protein 5 // 12 C1|12 22.16 cM // 11855 / Arhgap5 0.00330272 2.01389NM_001164173 // Cpsf1 // cleavage and polyadenylation specific factor 1 // 15 D3|15 // Cpsf1 6.13E-07 2.01401--- 0.000474149 2.01405NM_001110251 // Hmbs // hydroxymethylbilane synthase // 9 A5.2|9 24.84 cM // 15288 /// Hmbs 0.00124563 2.01489NM_001190984 // Lancl1 // LanC (bacterial lantibiotic synthetase component C)-like 1 // Lancl1 0.0025499 2.01496NM_001130150 // Arhgef1 // Rho guanine nucleotide exchange factor (GEF) 1 // 7 A3|7 // Arhgef1 2.94E-05 2.01573--- 0.00317865 2.01612NM_145415 // Diexf // digestive organ expansion factor homolog (zebrafish) // 1 H6|1 // Diexf 9.06E-05 2.01636NR_027897 // 0610012G03Rik // RIKEN cDNA 0610012G03 gene // 16 B2|16 // 106264 /// BC02 0610012G03Rik 0.000177354 2.01706NM_175528 // E330009J07Rik // RIKEN cDNA E330009J07 gene // 6 B1|6 // 243780 /// ENSMUS E330009J07Rik 0.00138016 2.01729NM_027810 // Bbs7 // Bardet-Biedl syndrome 7 (human) // 3 B|3 // 71492 /// ENSMUST00000 Bbs7 0.000379042 2.0173NM_008563 // Mcm3 // minichromosome maintenance deficient 3 (S. cerevisiae) // 1|1 A3-A Mcm3 5.32E-05 2.01778--- 0.000671249 2.01882NM_023831 // Ift46 // intraflagellar transport 46 // 9 A5.2|9 // 76568 /// XM_006510671 Ift46 0.00010633 2.0195NM_153116 // Gtpbp10 // GTP-binding protein 10 (putative) // 5 A1|5 // 207704 /// ENSMU Gtpbp10 0.00149369 2.02064NM_001033298 // Kiz // kizuna centrosomal protein // 2 G2|2 // 228730 /// XM_006499299 Kiz 0.00051476 2.02147ENSMUST00000145438 // 2810008D09Rik // RIKEN cDNA 2810008D09 gene // 11|11 // 76972 /// 2810008D09Rik 0.00195971 2.02275NM_145466 // Ggact // gamma-glutamylamine cyclotransferase // 14 E5|14 // 223267 /// XM Ggact 0.00175495 2.02312NM_025615 // 2810004N23Rik // RIKEN cDNA 2810004N23 gene // 8 E2|8 // 66523 /// ENSMUST 2810004N23Rik 0.00350684 2.02376NM_001291031 // Ap5s1 // adaptor-related protein 5 complex, sigma 1 subunit // 2|2 F3 / Ap5s1 0.000454111 2.02413NM_026246 // Mrpl49 // mitochondrial ribosomal protein L49 // 19 A|19 4.34 cM // 18120 Mrpl49 2.31E-05 2.02513NM_001253904 // Ncor2 // nuclear receptor co-repressor 2 // 5 F|5 // 20602 /// NM_00125 Ncor2 0.000292298 2.02536NM_133227 // Nup155 // nucleoporin 155 // 15|15 A2 // 170762 /// XM_006519972 // Nup155 Nup155 4.90E-06 2.02596NM_001162855 // Nsmce4a // non-SMC element 4 homolog A (S. cerevisiae) // 7 F3|7 // 678 Nsmce4a 5.78E-07 2.02611NM_001285997 // Prc1 // protein regulator of cytokinesis 1 // 7 D3|7 45.62 cM // 233406 Prc1 0.000341345 2.02648NM_009086 // Polr1b // polymerase (RNA) I polypeptide B // 2 F3|2 // 20017 /// ENSMUST0 Polr1b 0.00677467 2.02694--- 0.00446899 2.02699NM_033320 // Glce // glucuronyl C5-epimerase // 9 C-D|9 // 93683 /// ENSMUST00000034785 Glce 0.000106523 2.02728NM_025346 // Rmnd5b // required for meiotic nuclear division 5 homolog B (S. cerevisiae Rmnd5b 2.25E-05 2.02731NM_172597 // Txndc16 // thioredoxin domain containing 16 // 14|14 C1 // 70561 /// XM_00 Txndc16 6.23E-05 2.02813NM_172809 // Sacs // sacsin // 14 D1|14 32.13 cM // 50720 /// ENSMUST00000089394 // Sac Sacs 0.0013325 2.0286NM_027334 // Mettl7a1 // methyltransferase like 7A1 // 15|15 F3 // 70152 /// XM_0065213 Mettl7a1 0.000353439 2.02964XM_006511927 // Ctnnb1 // catenin (cadherin associated protein), beta 1 // 9 F4|9 72.19 Ctnnb1 1.61E-06 2.03066NM_008961 // Pter // phosphotriesterase related // 2 A1|2 // 19212 /// XM_006497400 // Pter 0.000413794 2.0308NM_021434 // Gpr180 // G protein-coupled receptor 180 // 14 E4|14 // 58245 /// ENSMUST0 Gpr180 0.000492318 2.03085NM_028320 // Adipor1 // adiponectin receptor 1 // 1 E4|1 // 72674 /// ENSMUST0000002772 Adipor1 1.57E-06 2.03199NM_178653 // Sccpdh // saccharopine dehydrogenase (putative) // 1 H4|1 // 109232 /// EN Sccpdh 0.000301652 2.03236NM_001146329 // Sbk2 // SH3-binding domain kinase family, member 2 // 7 A1|7 // 381836 Sbk2 0.0022511 2.03257NM_177741 // Ppp1r3b // protein phosphatase 1, regulatory (inhibitor) subunit 3B // 8 A Ppp1r3b 0.0023323 2.0326--- 0.00149888 2.03284NM_177721 // Ranbp6 // RAN binding protein 6 // 19 C1|19 // 240614 /// ENSMUST000000995 Ranbp6 0.00330545 2.03376--- 0.00616102 2.03382NM_027456 // Armc9 // armadillo repeat containing 9 // 1 C5|1 // 78795 /// NM_030184 // Armc9 0.00185325 2.03489

NM_021028 // Tk2 // thymidine kinase 2, mitochondrial // 8 D3|8 // 57813 /// NR_045642 Tk2 5.15E-05 2.03683NM_177843 // Gm14461 // predicted gene 14461 // 2 C3|2 // 329436 /// ENSMUST00000067618 Gm14461 0.00526977 2.03773NM_009194 // Slc12a2 // solute carrier family 12, member 2 // 18 D3|18 32.15 cM // 2049 Slc12a2 0.000178564 2.03797ENSMUST00000052645 // Nudt6 // nudix (nucleoside diphosphate linked moiety X)-type moti Nudt6 0.000324925 2.03826NM_001252547 // Sh2d3c // SH2 domain containing 3C // 2 B|2 // 27387 /// NM_013781 // S Sh2d3c 0.000120945 2.03827--- 7.75E-05 2.03904NM_025642 // Mis18a // MIS18 kinetochore protein homolog A (S. pombe) // 16 C3.3|16 // Mis18a 6.81E-05 2.03934NM_009690 // Cd5l // CD5 antigen-like // 3 F1|3 // 11801 /// ENSMUST00000015998 // Cd5l Cd5l 1.23E-05 2.03975NM_133719 // Metrn // meteorin, glial cell differentiation regulator // 17 A3.3|17 // 7 Metrn 0.00103921 2.03983NM_009791 // Aspm // asp (abnormal spindle)-like, microcephaly associated (Drosophila) Aspm 0.00663184 2.0402NM_020584 // Terf2ip // telomeric repeat binding factor 2, interacting protein // 8 E1| Terf2ip 0.000179223 2.04063NM_001114339 // Pank1 // pantothenate kinase 1 // 19 G1-G3|19 // 75735 /// NM_023792 // Pank1 1.13E-05 2.04117NM_183186 // Foxn3 // forkhead box N3 // 12 E|12 // 71375 /// XM_006516236 // Foxn3 // Foxn3 3.40E-05 2.04144NM_172151 // Zdhhc8 // zinc finger, DHHC domain containing 8 // 16 A3|16 11.29 cM // 27 Zdhhc8 0.000516 2.04164NM_011274 // Uri1 // URI1, prefoldin-like chaperone // 7 B2|7 // 19777 /// XM_006539676 Uri1 0.00015379 2.04273--- 0.00132579 2.04276NM_009663 // Alox5ap // arachidonate 5-lipoxygenase activating protein // 5 G3|5 // 116 Alox5ap 2.44E-07 2.04283NM_001243741 // C87436 // expressed sequence C87436 // 6 D1|6 // 232196 /// XM_00650597 C87436 0.00120011 2.04332NM_009272 // Srm // spermidine synthase // 4 E2|4 // 20810 /// ENSMUST00000006611 // Sr Srm 0.000207993 2.04374NM_001164480 // Sipa1 // signal-induced proliferation associated gene 1 // 19 A|19 4.34 Sipa1 8.83E-05 2.04418NM_018889 // Pigb // phosphatidylinositol glycan anchor biosynthesis, class B // 9 D|9 Pigb 5.41E-05 2.04471NM_019993 // Aldh9a1 // aldehyde dehydrogenase 9, subfamily A1 // 1|1 H2 // 56752 /// X Aldh9a1 5.93E-06 2.04475NM_198607 // Them6 // thioesterase superfamily member 6 // 15|15 E1 // 223626 /// ENSMU Them6 0.00674648 2.04514NR_028564 // Snord95 // small nucleolar RNA, C/D box 95 // 11|11 // 100216540 /// ENSMU Snord95 0.00376783 2.04541NM_198306 // Galnt9 // UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosa Galnt9 0.000895172 2.04544NM_001290181 // Nudt7 // nudix (nucleoside diphosphate linked moiety X)-type motif 7 // Nudt7 0.000550697 2.04786ENSMUST00000109020 // Gm14440 // predicted gene 14440 // 2|2 // 100503353 /// ENSMUST00 Gm14440 3.32E-06 2.04805NM_028410 // Prkrir // protein-kinase, interferon-inducible double stranded RNA depende Prkrir 0.000206564 2.04846NM_027206 // Tnfaip8l2 // tumor necrosis factor, alpha-induced protein 8-like 2 // 3 F2 Tnfaip8l2 4.13E-05 2.04932NM_013512 // Epb4.1l4a // erythrocyte protein band 4.1-like 4a // 18 B1|18 // 13824 /// Epb4.1l4a 0.000142722 2.04958NM_001252316 // Shmt2 // serine hydroxymethyltransferase 2 (mitochondrial) // 10 D3|10 Shmt2 0.000585282 2.05001NM_001206335 // Itfg3 // integrin alpha FG-GAP repeat containing 3 // 17 A3.3|17 // 106 Itfg3 1.97E-06 2.05072XM_006514336 // Dtx3 // deltex 3 homolog (Drosophila) // 10 D3|10 // 80904 /// ENSMUST0 Dtx3 1.48E-05 2.05177NM_001199188 // Snx5 // sorting nexin 5 // 2 H1|2 70.98 cM // 69178 /// NM_024225 // Sn Snx5 3.19E-07 2.05189NM_028101 // Jmjd8 // jumonji domain containing 8 // 17|17 B1 // 72106 /// ENSMUST00000 Jmjd8 0.000112736 2.05312NM_009811 // Casp6 // caspase 6 // 3|3 H1 // 12368 /// ENSMUST00000029626 // Casp6 // c Casp6 0.000922718 2.05338NM_173757 // Mrps27 // mitochondrial ribosomal protein S27 // 13 D1|13 // 218506 /// EN Mrps27 0.000501275 2.05383NM_001168240 // Irak1bp1 // interleukin-1 receptor-associated kinase 1 binding protein Irak1bp1 0.000118358 2.05435NM_024248 // Cars2 // cysteinyl-tRNA synthetase 2 (mitochondrial)(putative) // 8|8 A2 / Cars2 2.49E-05 2.05467NM_026632 // Rpa3 // replication protein A3 // 6 A1|6 // 68240 /// XM_885368 // Gm6195 Rpa3 0.00533654 2.05527ENSMUST00000132370 // 4933439K11Rik // RIKEN cDNA 4933439K11 gene // 1|1 // 71319 /// E 4933439K11Rik 0.00246676 2.05572NR_027866 // 5730408K05Rik // RIKEN cDNA 5730408K05 gene // 19|19 // 67531 /// NR_03959 5730408K05Rik 0.00255158 2.0565NM_028314 // 2700097O09Rik // RIKEN cDNA 2700097O09 gene // 12 C1|12 // 72658 /// NR_03 2700097O09Rik 0.00329389 2.05689NM_001163241 // Nqo2 // NAD(P)H dehydrogenase, quinone 2 // 13 A4|13 14.01 cM // 18105 Nqo2 7.38E-05 2.05743NM_029701 // Spcs3 // signal peptidase complex subunit 3 homolog (S. cerevisiae) // 8 B Spcs3 1.06E-05 2.05771NM_026430 // Uxs1 // UDP-glucuronate decarboxylase 1 // 1 C1.1|1 // 67883 /// XM_006496 Uxs1 0.00168531 2.05857NM_013865 // Ndrg3 // N-myc downstream regulated gene 3 // 2 H1|2 // 29812 /// NM_18095 Ndrg3 1.59E-06 2.05864NM_001163819 // Fance // Fanconi anemia, complementation group E // 17 A3.3|17 // 72775 Fance 0.00454727 2.05989NM_172770 // Ttc12 // tetratricopeptide repeat domain 12 // 9 A5.3|9 // 235330 /// ENSM Ttc12 4.83E-07 2.05993NM_080793 // Setd7 // SET domain containing (lysine methyltransferase) 7 // 3 C|3 // 73 Setd7 0.000144995 2.06009NM_001134384 // Iqsec1 // IQ motif and Sec7 domain 1 // 6 D1|6 40.16 cM // 232227 /// X Iqsec1 0.000160105 2.06011NM_139236 // Nol6 // nucleolar protein family 6 (RNA-associated) // 4 A5|4 // 230082 // Nol6 4.97E-06 2.06256NM_172742 // Mtmr10 // myotubularin related protein 10 // 7 C|7 // 233315 /// ENSMUST00 Mtmr10 6.84E-06 2.06281NM_001164420 // Pqlc1 // PQ loop repeat containing 1 // 18 E3|18 // 66943 /// NM_001164 Pqlc1 3.69E-06 2.06306NM_145624 // Zfp709 // zinc finger protein 709 // 8 B3.3|8 // 236193 Zfp709 0.0025292 2.06322NM_011947 // Map3k3 // mitogen-activated protein kinase kinase kinase 3 // 11 E1|11 // Map3k3 1.31E-06 2.06378XM_006541085 // 2410002F23Rik // RIKEN cDNA 2410002F23 gene // 7 B4|7 // 668661 /// ENS 2410002F23Rik 7.01E-06 2.06532NM_001276446 // Alad // aminolevulinate, delta-, dehydratase // 4 B3|4 33.17 cM // 1702 Alad 0.000323114 2.06534NM_011912 // Vax2 // ventral anterior homeobox 2 // 6 C3|6 35.94 cM // 24113 /// ENSMUS Vax2 0.00540525 2.06665NM_008892 // Pola1 // polymerase (DNA directed), alpha 1 // X C-D|X 41.06 cM // 18968 / Pola1 0.000540421 2.0667NM_001163126 // Cog5 // component of oligomeric golgi complex 5 // 12 A2|12 // 238123 / Cog5 5.67E-07 2.06733ENSMUST00000181224 // AU020206 // expressed sequence AU020206 // --- // --- /// AK04941 AU020206 4.75E-08 2.06781NM_026796 // Smyd2 // SET and MYND domain containing 2 // 1 H6|1 // 226830 /// XM_00649 Smyd2 0.000484335 2.06822NM_001082476 // Ndor1 // NADPH dependent diflavin oxidoreductase 1 // 2 A3|2 // 78797 / Ndor1 7.29E-06 2.06836NM_001285980 // Skp2 // S-phase kinase-associated protein 2 (p45) // 15 A2|15 // 27401 Skp2 2.81E-05 2.0691NM_009478 // Urod // uroporphyrinogen decarboxylase // 4 D1|4 53.41 cM // 22275 /// XM_ Urod 1.80E-05 2.06967NM_029115 // Ccdc181 // coiled-coil domain containing 181 // 1|1 H1 // 74895 /// ENSMUS Ccdc181 0.0003442 2.07005--- 0.00196138 2.07008XM_006497827 // Surf2 // surfeit gene 2 // 2 A3|2 19.1 cM // 20931 /// ENSMUST000000150 Surf2 4.20E-06 2.07011NM_001286544 // Ccpg1 // cell cycle progression 1 // 9 D|9 40.08 cM // 72278 /// ENSMUS Ccpg1 0.000221482 2.07103NM_023733 // Crot // carnitine O-octanoyltransferase // 5 A1|5 // 74114 /// ENSMUST0000 Crot 1.17E-05 2.07292ENSMUST00000103130 // Dsn1 // DSN1, MIND kinetochore complex component, homolog (S. cer Dsn1 0.00592051 2.07347NM_028284 // Bbs5 // Bardet-Biedl syndrome 5 (human) // 2|2 C3 // 72569 /// ENSMUST0000 Bbs5 7.35E-05 2.07428NM_026268 // Dusp6 // dual specificity phosphatase 6 // 10|10 C3 // 67603 /// ENSMUST00 Dusp6 7.00E-07 2.07564NM_001285893 // Vps8 // vacuolar protein sorting 8 homolog (S. cerevisiae) // 16 B1|16 Vps8 1.05E-06 2.07567NM_025671 // Ogfod2 // 2-oxoglutarate and iron-dependent oxygenase domain containing 2 Ogfod2 0.00380381 2.07587NR_045299 // 2900076A07Rik // RIKEN cDNA 2900076A07 gene // 7 D1|7 // 100504421 /// ENS 2900076A07Rik 0.00169859 2.0764NM_026046 // Zfp329 // zinc finger protein 329 // 7|7 A2 // 67230 /// ENSMUST0000007222 Zfp329 8.53E-05 2.07737NM_133683 // Tmem19 // transmembrane protein 19 // 10 D2|10 // 67226 /// XM_006513974 / Tmem19 0.000287076 2.0779NM_025677 // Tsen15 // tRNA splicing endonuclease 15 homolog (S. cerevisiae) // 1 G3|1 Tsen15 0.00345878 2.0787NM_001293791 // Ints10 // integrator complex subunit 10 // 8|8 C1 // 70885 /// NM_00129 Ints10 1.26E-05 2.07961NM_199068 // Foxk1 // forkhead box K1 // 5 G2|5 81.53 cM // 17425 /// ENSMUST0000007283 Foxk1 0.000885948 2.08063NM_183046 // Kif20b // kinesin family member 20B // 19 C2|19 // 240641 /// ENSMUST00000 Kif20b 6.74E-05 2.08068NM_001005860 // Clec4a4 // C-type lectin domain family 4, member a4 // 6 F2|6 // 474145 Clec4a4 0.000156672 2.08147NM_001099349 // Gm14308 // predicted gene 14308 // 2 H4|2 // 100043381 /// NM_001100415 Gm14308 1.64E-07 2.0818NM_028634 // Cby1 // chibby homolog 1 (Drosophila) // 15 E2|15 // 73739 /// XM_00652148 Cby1 0.000104668 2.0821NM_026044 // Dph7 // diphthamine biosynethesis 7 // 2 A3|2 // 67228 /// XM_006498242 // Dph7 0.00394214 2.08439NM_001285991 // Tbc1d5 // TBC1 domain family, member 5 // 17 C|17 // 72238 /// NM_00128 Tbc1d5 4.54E-05 2.0846NM_019998 // Alg2 // asparagine-linked glycosylation 2 (alpha-1,3-mannosyltransferase) Alg2 6.57E-06 2.08537NM_001285487 // Mknk1 // MAP kinase-interacting serine/threonine kinase 1 // 4 D1|4 // Mknk1 6.15E-05 2.08558NM_008513 // Lrp5 // low density lipoprotein receptor-related protein 5 // 19|19 B // 1 Lrp5 0.000139443 2.0871NM_001110350 // Sin3a // transcriptional regulator, SIN3A (yeast) // 9 B|9 30.89 cM // Sin3a 2.06E-05 2.08713NM_011630 // Nr2c2 // nuclear receptor subfamily 2, group C, member 2 // 6 D1|6 // 2202 Nr2c2 4.75E-05 2.08742

NM_001289630 // Mgme1 // mitochondrial genome maintainance exonuclease 1 // 2|2 H1 // 7 Mgme1 0.00104106 2.08759NM_199198 // Hdac10 // histone deacetylase 10 // 15 E3|15 // 170787 /// NR_028447 // Hd Hdac10 0.00182919 2.09027NM_010864 // Myo5a // myosin VA // 9 D|9 42.26 cM // 17918 /// ENSMUST00000123128 // My Myo5a 3.76E-07 2.09041NM_010322 // Gnpat // glyceronephosphate O-acyltransferase // 8 E2|8 72.81 cM // 14712 Gnpat 2.38E-06 2.09155XM_006530467 // 2210016L21Rik // RIKEN cDNA 2210016L21 gene // 5 F|5 // 72357 /// ENSMU 2210016L21Rik 6.61E-05 2.09285NM_001008502 // Bbs12 // Bardet-Biedl syndrome 12 (human) // 3 B|3 // 241950 /// NM_001 Bbs12 0.00473768 2.09307ENSMUST00000146409 // Slc26a2 // solute carrier family 26 (sulfate transporter), member Slc26a2 0.000270096 2.09311NM_025411 // Pithd1 // PITH (C-terminal proteasome-interacting domain of thioredoxin-li Pithd1 0.00410308 2.09327NM_019482 // Panx1 // pannexin 1 // 9 A2|9 // 55991 /// ENSMUST00000056755 // Panx1 // Panx1 2.13E-06 2.09333NM_001293630 // Slc37a4 // solute carrier family 37 (glucose-6-phosphate transporter), Slc37a4 0.000343175 2.09421NM_008026 // Fli1 // Friend leukemia integration 1 // 9 A4|9 17.74 cM // 14247 /// XM_0 Fli1 4.64E-06 2.09437NM_001277898 // Prkaca // protein kinase, cAMP dependent, catalytic, alpha // 8|8 C3 // Prkaca 2.18E-05 2.09482NM_008702 // Nlk // nemo like kinase // 11 B5|11 // 18099 /// ENSMUST00000142739 // Nlk Nlk 2.56E-06 2.09501NM_130449 // Colec12 // collectin sub-family member 12 // 18 A1|18 // 140792 /// ENSMUS Colec12 1.19E-06 2.09764ENSMUST00000120226 // Cdk4 // cyclin-dependent kinase 4 // 10 D3|10 // 12567 /// ENSMUS Cdk4 3.93E-07 2.09805NM_001293800 // Ocel1 // occludin/ELL domain containing 1 // 8|8 C1 // 77090 /// NM_029 Ocel1 0.000306017 2.09825NM_008149 // Gpam // glycerol-3-phosphate acyltransferase, mitochondrial // 19 D2|19 50 Gpam 0.000395016 2.0985NM_175563 // Prr11 // proline rich 11 // 11 C|11 // 270906 /// ENSMUST00000051395 // Pr Prr11 0.00224667 2.09912NM_025659 // Abi3 // ABI gene family, member 3 // 11 D|11 // 66610 /// XM_006533953 // Abi3 8.34E-05 2.09944NM_179203 // Atad3a // ATPase family, AAA domain containing 3A // 4 E2|4 // 108888 /// Atad3a 0.000519508 2.09949NM_025904 // Yae1d1 // Yae1 domain containing 1 // 13 A2-A3|13 // 67008 /// ENSMUST0000 Yae1d1 0.00384275 2.09996NM_025812 // Hmg20a // high mobility group 20A // 9|9 C // 66867 /// XM_006511368 // Hm Hmg20a 9.06E-06 2.10144NM_001167994 // Trmt2b // TRM2 tRNA methyltransferase 2B // X E3|X // 215201 /// NM_172 Trmt2b 8.89E-05 2.10163NM_001136090 // Poli // polymerase (DNA directed), iota // 18 E2|18 44.48 cM // 26447 / Poli 5.38E-05 2.10219NM_009875 // Cdkn1b // cyclin-dependent kinase inhibitor 1B // 6 G1|6 65.77 cM // 12576 Cdkn1b 3.83E-06 2.10462NM_008354 // Il12rb2 // interleukin 12 receptor, beta 2 // 6 C1|6 30.81 cM // 16162 /// Il12rb2 0.00649988 2.10518NM_001099327 // Gm14305 // predicted gene 14305 // 2 H4|2 // 100043387 /// NM_001099349 Gm14305 8.18E-08 2.10667NM_008234 // Hells // helicase, lymphoid specific // 19|19 C3-D1 // 15201 /// XM_006526 Hells 0.000788542 2.10724NM_013546 // Hebp1 // heme binding protein 1 // 6 G1|6 // 15199 /// ENSMUST00000045855 Hebp1 2.03E-06 2.10745XM_006509478 // 4933411K20Rik // RIKEN cDNA 4933411K20 gene // 8 B2|8 26.16 cM // 66756 4933411K20Rik 8.86E-05 2.10829NM_025633 // Metap1d // methionyl aminopeptidase type 1D (mitochondrial) // 2 C2|2 // 6 Metap1d 0.000392636 2.10904NM_010517 // Igfbp4 // insulin-like growth factor binding protein 4 // 11 D|11 // 16010 Igfbp4 4.72E-05 2.10976NM_016658 // Galt // galactose-1-phosphate uridyl transferase // 4 A5|4 22.07 cM // 144 Galt 0.000672783 2.11001ENSMUST00000119830 // Zfp740 // zinc finger protein 740 // 15 F3|15 // 68744 /// ENSMUS Zfp740 3.83E-06 2.11039--- 0.00126946 2.11054XM_006504587 // Nxpe5 // neurexophilin and PC-esterase domain family, member 5 // 5 G2| Nxpe5 0.00283739 2.1123NM_175274 // Ttyh3 // tweety homolog 3 (Drosophila) // 5 G2|5 // 78339 /// XM_006504768 Ttyh3 5.00E-05 2.11259NM_028014 // 2310067B10Rik // RIKEN cDNA 2310067B10 gene // 11 E2|11 // 71947 /// XM_00 2310067B10Rik 0.00101779 2.11295NM_010167 // Eya4 // eyes absent 4 homolog (Drosophila) // 10 A3|10 10.44 cM // 14051 / Eya4 0.0001909 2.1133NM_001252472 // Cd84 // CD84 antigen // 1 H3|1 79.54 cM // 12523 /// NM_001289470 // Cd Cd84 1.10E-09 2.1142NM_009687 // Apex1 // apurinic/apyrimidinic endonuclease 1 // 14 C3|14 26.3 cM // 11792 Apex1 0.000457217 2.11566NM_028404 // Top1mt // DNA topoisomerase 1, mitochondrial // 15|15 E1 // 72960 /// XR_3 Top1mt 0.000780064 2.11636NM_011895 // Slc35a1 // solute carrier family 35 (CMP-sialic acid transporter), member Slc35a1 8.22E-05 2.11678NM_001033490 // Pusl1 // pseudouridylate synthase-like 1 // 4 E2|4 87.66 cM // 433813 / Pusl1 0.000591933 2.1169NM_001252494 // Rapgef6 // Rap guanine nucleotide exchange factor (GEF) 6 // 11 B1.3|11 Rapgef6 0.000167563 2.11694NM_023045 // Xpo7 // exportin 7 // 14 D2|14 // 65246 /// ENSMUST00000022696 // Xpo7 // Xpo7 2.86E-06 2.11775NM_001099349 // Gm14308 // predicted gene 14308 // 2 H4|2 // 100043381 /// NM_001100415 Gm14308 9.97E-08 2.11811NM_001099349 // Gm14308 // predicted gene 14308 // 2 H4|2 // 100043381 /// NM_001100415 Gm14308 9.97E-08 2.11811NM_001290376 // Camk1d // calcium/calmodulin-dependent protein kinase ID // 2 A1|2 // 2 Camk1d 1.50E-05 2.11841NM_008564 // Mcm2 // minichromosome maintenance deficient 2 mitotin (S. cerevisiae) // Mcm2 0.00155687 2.11973ENSMUST00000081879 // St6galnac6 // ST6 (alpha-N-acetyl-neuraminyl-2,3-beta-galactosyl- St6galnac6 0.00238953 2.11979NM_022980 // Rcan3 // regulator of calcineurin 3 // 4 D3|4 67.59 cM // 53902 /// ENSMUS Rcan3 0.000128625 2.11989NM_028015 // Cers5 // ceramide synthase 5 // 15 F1|15 // 71949 /// ENSMUST00000023762 / Cers5 1.64E-05 2.12197NM_008323 // Idh3g // isocitrate dehydrogenase 3 (NAD+), gamma // X A7.3-B|X 37.41 cM / Idh3g 2.70E-07 2.12238NM_011496 // Aurkb // aurora kinase B // 11 B3|11 42.32 cM // 20877 /// ENSMUST00000021 Aurkb 0.00224147 2.12455--- 0.00387433 2.12612NM_010832 // Msl3 // male-specific lethal 3 homolog (Drosophila) // X F5|X // 17692 /// Msl3 0.000316862 2.12732NM_009761 // Bnip3l // BCL2/adenovirus E1B interacting protein 3-like // 14 D1|14 34.6 Bnip3l 6.75E-07 2.12772NM_001168541 // Tsku // tsukushi // 7 E2|7 // 244152 /// ENSMUST00000094161 // Tsku // Tsku 6.44E-06 2.12842NM_001111311 // Lrrfip1 // leucine rich repeat (in FLII) interacting protein 1 // 1 D|1 Lrrfip1 1.28E-05 2.12896NM_007624 // Cbx3 // chromobox 3 // 6 B-C|6 24.89 cM // 12417 /// XM_006544713 // LOC10 Cbx3 0.0016918 2.12913NM_144550 // Spice1 // spindle and centriole associated protein 1 // 16 B4|16 28.67 cM Spice1 8.57E-05 2.1292ENSMUST00000031420 // Gpn3 // GPN-loop GTPase 3 // 5 F|5 62.33 cM // 68080 /// ENSMUST0 Gpn3 0.00050402 2.12955NM_172513 // Fam126b // family with sequence similarity 126, member B // 1 C1.3|1 29.12 Fam126b 1.96E-05 2.12968NM_013872 // Pmm1 // phosphomannomutase 1 // 15 E1|15 // 29858 /// XM_006521064 // Pmm1 Pmm1 0.000290794 2.13125AK021184 // Adam10 // a disintegrin and metallopeptidase domain 10 // 9 D|9 39.53 cM // Adam10 0.00319194 2.13195AK021184 // Adam10 // a disintegrin and metallopeptidase domain 10 // 9 D|9 39.53 cM // Adam10 0.00319194 2.13195NM_145437 // Cd300ld // CD300 molecule-like family member d // 11 E2|11 // 217305 /// E Cd300ld 4.33E-05 2.13267NM_001195529 // Gm4980 // predicted gene 4980 // 7 E2|7 // 100503386 /// ENSMUST0000017 Gm4980 0.0029247 2.13349--- 0.00491304 2.13405NR_040613 // Acss2os // acyl-CoA synthetase short-chain family member 2, opposite stran Acss2os 0.000526031 2.13553NR_038162 // Stamos // signal transducing adaptor molecule (SH3 domain and ITAM motif) Stamos 0.00622194 2.13556NM_001253812 // Elp3 // elongator acetyltransferase complex subunit 3 // 14 D1|14 // 74 Elp3 2.05E-06 2.13697NM_001290570 // Ralgps1 // Ral GEF with PH domain and SH3 binding motif 1 // 2 B|2 // 2 Ralgps1 0.000233148 2.13738ENSMUST00000000199 // Ncs1 // neuronal calcium sensor 1 // 2 B|2 // 14299 /// NM_019681 Ncs1 0.00504038 2.13738NM_001112711 // Grk6 // G protein-coupled receptor kinase 6 // 13 B1-3|13 30.06 cM // 2 Grk6 0.000131176 2.13771--- 0.00119673 2.13962NM_001276288 // Aes // amino-terminal enhancer of split // 10 C1|10 39.72 cM // 14797 / Aes 7.26E-06 2.1399ENSMUST00000104456 // Gm24982 // predicted gene, 24982 // --- // --- Gm24982 0.000532037 2.14081NM_030174 // Mctp1 // multiple C2 domains, transmembrane 1 // 13 C1|13 // 78771 /// ENS Mctp1 6.23E-05 2.14114NM_023209 // Pbk // PDZ binding kinase // 14 D1|14 34.36 cM // 52033 /// XM_006519257 / Pbk 0.000280356 2.14172NM_145140 // Abcc10 // ATP-binding cassette, sub-family C (CFTR/MRP), member 10 // 17 C Abcc10 0.00272104 2.14221NM_029926 // Irak4 // interleukin-1 receptor-associated kinase 4 // 15 F1|15 // 266632 Irak4 8.41E-07 2.14303NM_001077698 // Fmnl1 // formin-like 1 // 11 D|11 // 57778 /// NM_019679 // Fmnl1 // fo Fmnl1 6.00E-05 2.14425XM_006516710 // Zscan26 // zinc finger and SCAN domain containing 26 // 13 A3.1|13 // 4 Zscan26 2.14E-05 2.14514NM_007415 // Parp1 // poly (ADP-ribose) polymerase family, member 1 // 1 H5|1 84.44 cM Parp1 1.31E-05 2.14574NM_001163319 // Tubgcp6 // tubulin, gamma complex associated protein 6 // 15 E3|15 // 3 Tubgcp6 0.00543569 2.14647NM_021793 // Tmem8 // transmembrane protein 8 (five membrane-spanning domains) // 17|17 Tmem8 1.80E-05 2.14664NM_001099327 // Gm14305 // predicted gene 14305 // 2 H4|2 // 100043387 /// NM_001099349 Gm14305 1.54E-07 2.14698NM_172749 // Zfp646 // zinc finger protein 646 // 7 F3|7 // 233905 /// ENSMUST000000503 Zfp646 7.06E-05 2.14779NM_011734 // Siae // sialic acid acetylesterase // 9 A4|9 20.79 cM // 22619 /// XM_0065 Siae 1.00E-06 2.14821XR_389000 // LOC102632994 // uncharacterized LOC102632994 // --- // 102632994 /// ENSMU LOC102632994 0.0052418 2.14825ENSMUST00000120450 // Gart // phosphoribosylglycinamide formyltransferase // 16 C3-C4|1 Gart 1.62E-05 2.14889

NM_001042541 // Akap1 // A kinase (PRKA) anchor protein 1 // 11 C|11 // 11640 /// NM_00 Akap1 0.000396127 2.14913NM_029348 // Zbtb4 // zinc finger and BTB domain containing 4 // 11|11 B4 // 75580 /// Zbtb4 0.00538992 2.14938NM_134024 // Tubg1 // tubulin, gamma 1 // 11 D|11 64.24 cM // 103733 /// ENSMUST0000004 Tubg1 0.000279669 2.14977NM_001081107 // Helq // helicase, POLQ-like // 5|5 E // 191578 /// XM_006534827 // Helq Helq 0.000195987 2.15003NM_138743 // Smim11 // small integral membrane protein 11 // 16 C4|16 // 68936 /// ENSM Smim11 0.00118299 2.15006NM_176976 // 5830418K08Rik // RIKEN cDNA 5830418K08 gene // 9 A2|9 // 319675 /// ENSMUS 5830418K08Rik 0.000465295 2.15046NM_001134829 // Lpgat1 // lysophosphatidylglycerol acyltransferase 1 // 1 H6|1 // 22685 Lpgat1 3.32E-05 2.15142NM_024288 // Rmnd5a // required for meiotic nuclear division 5 homolog A (S. cerevisiae Rmnd5a 0.000118481 2.15258NM_010489 // Hyal2 // hyaluronoglucosaminidase 2 // 9 F1|9 58.12 cM // 15587 /// XM_006 Hyal2 1.51E-06 2.1539NM_144872 // Eml3 // echinoderm microtubule associated protein like 3 // 19 A|19 // 225 Eml3 0.0005523 2.15552XR_374487 // Knstrn // kinetochore-localized astrin/SPAG5 binding // 2 E5|2 // 51944 // Knstrn 0.000173306 2.15621NM_028354 // Tdp1 // tyrosyl-DNA phosphodiesterase 1 // 12 E|12 // 104884 /// XM_006515 Tdp1 4.91E-07 2.15678NM_001166642 // Bcas3 // breast carcinoma amplified sequence 3 // 11 C|11 // 192197 /// Bcas3 2.98E-05 2.15706NM_025954 // Pgp // phosphoglycolate phosphatase // 17 A3.3|17 // 67078 /// ENSMUST0000 Pgp 0.00409265 2.15812BC068155 // Plxna2 // plexin A2 // 1 H6|1 // 18845 /// NM_008882 // Plxna2 // plexin A2 Plxna2 4.37E-05 2.15835NM_198425 // Eid2 // EP300 interacting inhibitor of differentiation 2 // 7 A3|7 // 3866 Eid2 3.82E-05 2.15918NM_177293 // Mtap7d3 // MAP7 domain containing 3 // X A5|X // 320923 /// XM_006528088 / Mtap7d3 0.00109856 2.16027NM_144907 // Sesn2 // sestrin 2 // 4 D2.3|4 // 230784 /// ENSMUST00000030724 // Sesn2 / Sesn2 0.00504931 2.16087--- 0.00647882 2.16113NM_181815 // Cep128 // centrosomal protein 128 // 12|12 E // 75216 /// XM_006516326 // Cep128 5.91E-05 2.16116NM_001081133 // Kif16b // kinesin family member 16B // 2|2 G3 // 16558 /// XM_006498813 Kif16b 2.48E-06 2.16117--- 0.00358553 2.16179NM_001177406 // Gm14431 // predicted gene 14431 // 2|2 // 100303732 /// NM_001177407 // Gm14431 2.16E-08 2.16189NM_178795 // Ppip5k1 // diphosphoinositol pentakisphosphate kinase 1 // 2 E5|2 // 32765 Ppip5k1 4.15E-05 2.16238NM_001254761 // Rnf128 // ring finger protein 128 // X F1|X // 66889 /// ENSMUST0000011 Rnf128 4.63E-06 2.16384NM_025693 // Tmem41a // transmembrane protein 41a // 16 B1|16 // 66664 /// NR_037773 // Tmem41a 0.000346161 2.16474XM_006530044 // Gm14434 // predicted gene 14434 // 2 H4|2 // 668039 /// NM_001099349 // Gm14434 3.07E-07 2.16539XM_006528794 // Ptchd1 // patched domain containing 1 // X F3|X // 211612 /// NM_001093 Ptchd1 0.000464764 2.16578ENSMUST00000028294 // Card9 // caspase recruitment domain family, member 9 // 2 A3|2 // Card9 3.05E-06 2.1663--- 0.000438346 2.16643NM_010620 // Kif15 // kinesin family member 15 // 9 F4|9 // 209737 /// ENSMUST000000407 Kif15 0.00128576 2.1669NM_001114660 // Scfd2 // Sec1 family domain containing 2 // 5 C3.3|5 // 212986 /// NM_0 Scfd2 0.000423854 2.16715NM_172772 // Fam63b // family with sequence similarity 63, member B // 9 D|9 // 235461 Fam63b 1.44E-05 2.16788NM_001030307 // Dkc1 // dyskeratosis congenita 1, dyskerin // X A7.3|X // 245474 /// EN Dkc1 0.000305457 2.16814NR_030716 // 5430417L22Rik // RIKEN cDNA 5430417L22 gene // 2 E5|2 // 100043272 /// ENS 5430417L22Rik 0.000737107 2.16818NM_026410 // Cdca5 // cell division cycle associated 5 // 19 A|19 // 67849 /// ENSMUST0 Cdca5 0.000200262 2.16828ENSMUST00000081455 // Gm6917 // predicted gene 6917 // 13 B3|13 // 628794 /// ENSMUST00 Gm6917 3.47E-06 2.16946ENSMUST00000158426 // Gm23354 // predicted gene, 23354 // --- // --- Gm23354 0.00556143 2.16997NM_146234 // Mmgt1 // membrane magnesium transporter 1 // X A5|X // 236792 /// ENSMUST0 Mmgt1 8.70E-05 2.17038NM_199199 // Tmem199 // transmembrane protein 199 // 11 B5|11 // 195040 /// ENSMUST0000 Tmem199 0.00578899 2.17049NM_001165980 // Dcaf17 // DDB1 and CUL4 associated factor 17 // 2 C2|2 // 75763 /// NM_ Dcaf17 2.25E-05 2.17051XM_006511191 // Zbtb38 // zinc finger and BTB domain containing 38 // 9 E3.3|9 // 24500 Zbtb38 0.00010485 2.1718NM_001163609 // Psma8 // proteasome (prosome, macropain) subunit, alpha type, 8 // 18|1 Psma8 0.0063109 2.17183NM_001177406 // Gm14431 // predicted gene 14431 // 2|2 // 100303732 /// NM_001177407 // Gm14431 1.86E-06 2.1722NM_001177406 // Gm14431 // predicted gene 14431 // 2|2 // 100303732 /// NM_001177407 // Gm14431 1.86E-06 2.1722ENSMUST00000141541 // Gm15503 // predicted gene 15503 // --- // --- /// XM_006508140 // Gm15503 0.000462012 2.17563NM_026420 // Paip2 // polyadenylate-binding protein-interacting protein 2 // 18 B2|18 / Paip2 0.000170774 2.17632NM_001199431 // Dnmt1 // DNA methyltransferase (cytosine-5) 1 // 9 A3|9 7.66 cM // 1343 Dnmt1 4.18E-05 2.17713NM_001271434 // Haghl // hydroxyacylglutathione hydrolase-like // 17 A3.3|17 // 68977 / Haghl 4.09E-06 2.17925NM_001113351 // Synj2 // synaptojanin 2 // 17 A2-A3.1|17 3.59 cM // 20975 /// NM_001113 Synj2 2.59E-06 2.17968NM_019403 // Rnf5 // ring finger protein 5 // 17 B1|17 18.18 cM // 54197 /// ENSMUST000 Rnf5 0.000249232 2.18221NM_181547 // Nostrin // nitric oxide synthase trafficker // 2 C2|2 // 329416 /// ENSMUS Nostrin 5.11E-06 2.18251NM_001123367 // Gm3448 // predicted gene 3448 // 17 A2|17 // 100041639 /// NM_001123368 Gm3448 0.000327416 2.18325ENSMUST00000157182 // Gm25559 // predicted gene, 25559 // --- // --- Gm25559 0.000946094 2.18368NM_134081 // Dnajc9 // DnaJ (Hsp40) homolog, subfamily C, member 9 // 14 A3|14 // 10867 Dnajc9 0.000203578 2.18397NM_008857 // Prkci // protein kinase C, iota // 3 A3|3 14.65 cM // 18759 /// ENSMUST000 Prkci 8.52E-05 2.18444NM_019730 // Nme3 // NME/NM23 nucleoside diphosphate kinase 3 // 17 A3.3|17 // 79059 // Nme3 0.000405222 2.18522NM_001024806 // Cebpz // CCAAT/enhancer binding protein zeta // 17 E3|17 // 12607 /// E Cebpz 8.12E-05 2.18535NM_015830 // Capn15 // calpain 15 // 17|17 A3 // 50817 /// XM_006524609 // Capn15 // ca Capn15 3.79E-05 2.18573NM_001102436 // Acbd5 // acyl-Coenzyme A binding domain containing 5 // 2 A3|2 // 74159 Acbd5 0.00010379 2.18591NM_001205095 // Gm4944 // predicted gene 4944 // 17 A3.3|17 // 240038 /// XM_006524228 Gm4944 0.00168223 2.18598NM_177909 // Slc9a9 // solute carrier family 9 (sodium/hydrogen exchanger), member 9 // Slc9a9 0.000214669 2.18793NM_134158 // AF251705 // cDNA sequence AF251705 // 11 E2|11 80.57 cM // 140497 /// ENSM AF251705 0.000354116 2.1883NM_134021 // Pnpo // pyridoxine 5-phosphate oxidase // 11 D|11 // 103711 /// ENSMUST000 Pnpo 0.000451702 2.18992NM_013909 // Fbxl6 // F-box and leucine-rich repeat protein 6 // 15 D3|15 // 30840 /// Fbxl6 0.000565449 2.19062NR_051998 // Ankzf1 // ankyrin repeat and zinc finger domain containing 1 // 1 C3|1 38. Ankzf1 0.0014877 2.19101NM_011623 // Top2a // topoisomerase (DNA) II alpha // 11 D|11 62.91 cM // 21973 /// ENS Top2a 2.56E-05 2.19166NM_025939 // Paics // phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoribo Paics 1.84E-05 2.19177NM_001205336 // Arap3 // ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 3 // 1 Arap3 0.00313628 2.1933NM_024290 // Tnfrsf23 // tumor necrosis factor receptor superfamily, member 23 // 7 F5| Tnfrsf23 0.00400155 2.19399NM_001033321 // Tmem231 // transmembrane protein 231 // 8 E1|8 // 234740 /// ENSMUST000 Tmem231 0.00271585 2.19446NM_025339 // Tmem42 // transmembrane protein 42 // 9 F4|9 73.52 cM // 66079 /// XM_0065 Tmem42 0.00578708 2.19518NM_011729 // Ercc5 // excision repair cross-complementing rodent repair deficiency, com Ercc5 0.00111937 2.19554NM_001039239 // Zfp808 // zinc finger protein 80 // 13 B3|13 // 630579 /// ENSMUST00000 Zfp808 3.51E-05 2.19684NM_178632 // Ints7 // integrator complex subunit 7 // 1 H6|1 // 77065 /// ENSMUST000000 Ints7 1.43E-07 2.19779ENSMUST00000056508 // Clcn3 // chloride channel 3 // 8 B3.1|8 30.9 cM // 12725 /// NM_0 Clcn3 0.00162925 2.19781NM_026276 // Aasdhppt // aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl tr Aasdhppt 9.60E-05 2.19939NM_030729 // Nckipsd // NCK interacting protein with SH3 domain // 9 F2|9 // 80987 /// Nckipsd 5.70E-05 2.19958XM_006506390 // Atf7ip // activating transcription factor 7 interacting protein // 6 G1 Atf7ip 0.00379499 2.19967NM_001081163 // Chsy1 // chondroitin sulfate synthase 1 // 7 C|7 // 269941 /// ENSMUST0 Chsy1 0.000342431 2.19967NM_001286663 // Ssbp1 // single-stranded DNA binding protein 1 // 6|6 B2 // 381760 /// Ssbp1 0.000269499 2.19996--- 0.00495451 2.20168NM_177699 // Fhod1 // formin homology 2 domain containing 1 // 8 D3|8 // 234686 /// ENS Fhod1 1.27E-05 2.20226NM_001276321 // Cyhr1 // cysteine and histidine rich 1 // 15|15 E1 // 54151 /// NM_0012 Cyhr1 6.27E-06 2.2024ENSMUST00000148217 // Gm15156 // predicted gene 15156 // --- // --- Gm15156 0.000182691 2.20256--- 0.000139825 2.20332NM_028189 // B3gnt3 // UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 3 // B3gnt3 0.000222206 2.20384NM_207245 // Zfp870 // zinc finger protein 870 // 17 B1|17 // 240066 /// XM_006524252 / Zfp870 0.00476602 2.20396NM_153555 // Dcaf8 // DDB1 and CUL4 associated factor 8 // 1 H3|1 79.54 cM // 98193 /// Dcaf8 5.14E-06 2.20411NM_001013379 // Zfp930 // zinc finger protein 930 // 8 B3.3|8 // 234358 Zfp930 0.00101409 2.2043NM_030026 // Mccc2 // methylcrotonoyl-Coenzyme A carboxylase 2 (beta) // 13 D1|13 // 78 Mccc2 0.000509551 2.20446NM_152814 // Zfp566 // zinc finger protein 566 // 7 B1|7 // 72556 /// ENSMUST0000008878 Zfp566 0.00476481 2.20529NM_001160399 // Ccdc112 // coiled-coil domain containing 112 // 18 C|18 // 240261 /// E Ccdc112 0.000350302 2.20631

--- 0.00050465 2.20714NM_172824 // Ccdc14 // coiled-coil domain containing 14 // 16 B3|16 // 239839 /// XM_00 Ccdc14 0.00391292 2.20811NM_026585 // Fam21 // family with sequence similarity 21 // 6 F1|6 53.76 cM // 28006 // Fam21 1.03E-06 2.2083NR_029440 // 2010320M18Rik // RIKEN cDNA 2010320M18 gene // 8|8 // 72093 /// BC051496 / 2010320M18Ri 0.00450527 2.20865NM_011923 // Angptl2 // angiopoietin-like 2 // 2 B|2 // 26360 /// ENSMUST00000004208 // Angptl2 2.26E-07 2.20869NM_028355 // Ndc1 // NDC1 transmembrane nucleoporin // 4 C7|4 // 72787 /// XM_006503423 Ndc1 1.19E-07 2.21024NM_009592 // Abcb7 // ATP-binding cassette, sub-family B (MDR/TAP), member 7 // X C-D|X Abcb7 8.73E-06 2.21064NM_144818 // Ncaph // non-SMC condensin I complex, subunit H // 2 F1|2 // 215387 /// EN Ncaph 0.00051106 2.21307NR_030738 // 2410006H16Rik // RIKEN cDNA 2410006H16 gene // 11 B2|11 // 69221 /// ENSMU 2410006H16Rik 0.000178403 2.21331NM_207225 // Hdac4 // histone deacetylase 4 // 1 D|1 // 208727 /// XM_006529302 // Hdac Hdac4 0.000536819 2.21382NM_030697 // Kank3 // KN motif and ankyrin repeat domains 3 // 17 B1|17 17.98 cM // 808 Kank3 0.000272749 2.21404NM_023431 // Mum1 // melanoma associated antigen (mutated) 1 // 10 C1|10 // 68114 /// X Mum1 0.000501448 2.2145NM_173011 // Idh2 // isocitrate dehydrogenase 2 (NADP+), mitochondrial // 7 D3|7 45.43 Idh2 4.63E-08 2.21564NM_007379 // Abca2 // ATP-binding cassette, sub-family A (ABC1), member 2 // 2 A2-B|2 1 Abca2 9.07E-07 2.21641NM_178641 // Inpp5f // inositol polyphosphate-5-phosphatase F // 7 F3|7 // 101490 /// E Inpp5f 0.000492964 2.21642NM_172580 // Acot6 // acyl-CoA thioesterase 6 // 12 D1|12 // 217700 /// ENSMUST00000056 Acot6 0.000848844 2.2169NM_001037725 // Fam117b // family with sequence similarity 117, member B // 1 C2|1 // 7 Fam117b 5.64E-06 2.21735--- 0.00665696 2.21754--- 0.00362506 2.21811NM_029992 // Tchp // trichoplein, keratin filament binding // 5 F|5 // 77832 /// ENSMUS Tchp 1.96E-05 2.21926NM_001113408 // Ldb1 // LIM domain binding 1 // 19 C3|19 38.75 cM // 16825 /// NM_01069 Ldb1 1.07E-08 2.21999NM_178605 // Nop16 // NOP16 nucleolar protein // 13 B1|13 28.83 cM // 28126 /// ENSMUST Nop16 0.00105787 2.2203ENSMUST00000097466 // Gm10521 // predicted gene 10521 // --- // 100038548 /// AK143847 Gm10521 0.00195344 2.22146NM_178652 // Supt3 // suppressor of Ty 3 // 17 B3|17 // 109115 /// XM_006523474 // Supt Supt3 9.61E-05 2.22168NM_001291105 // E2f1 // E2F transcription factor 1 // 2 H1|2 76.79 cM // 13555 /// NM_0 E2f1 0.000437263 2.22186--- 0.00583275 2.22284NM_001081151 // Gan // giant axonal neuropathy // 8 E1|8 // 209239 /// ENSMUST000000644 Gan 0.000742961 2.22364--- 0.000105681 2.22526NM_144500 // Osbpl2 // oxysterol binding protein-like 2 // 2 H4|2 // 228983 /// ENSMUST Osbpl2 3.24E-08 2.22571NM_146106 // Lyplal1 // lysophospholipase-like 1 // 1 H5|1 // 226791 /// ENSMUST0000004 Lyplal1 9.39E-05 2.22776XM_006504522 // Wbscr27 // Williams Beuren syndrome chromosome region 27 (human) // 5 G Wbscr27 0.000913608 2.22789NM_146261 // Fam199x // family with sequence similarity 199, X-linked // X F1|X // 2456 Fam199x 0.000111569 2.2287NM_016683 // Zkscan5 // zinc finger with KRAB and SCAN domains 5 // 5 G2|5 // 22757 /// Zkscan5 0.000176709 2.22872NM_033270 // E2f6 // E2F transcription factor 6 // 12 A1.1|12 8.04 cM // 50496 /// NR_0 E2f6 2.26E-05 2.22886--- 0.0061704 2.22923NM_008898 // Por // P450 (cytochrome) oxidoreductase // 5 G2|5 75.34 cM // 18984 /// XM Por 1.89E-06 2.22933ENSMUST00000023262 // Gm9747 // predicted gene 9747 // --- // --- /// AY169784 // Irs1 Gm9747 6.83E-05 2.22959--- 0.00521277 2.22967NM_027117 // Klhdc2 // kelch domain containing 2 // 12 C3|12 28.77 cM // 69554 /// ENSM Klhdc2 1.35E-06 2.23199NM_008537 // Amacr // alpha-methylacyl-CoA racemase // 15|15 B1 // 17117 /// ENSMUST000 Amacr 0.0025185 2.23207NR_039562 // Mir5103 // microRNA 5103 // 1|1 13.22 cM // 100628580 /// ENSMUST000001751 Mir5103 1.59E-05 2.23291--- 0.00608848 2.23365NM_144942 // Csad // cysteine sulfinic acid decarboxylase // 15 F3|15 // 246277 /// XM_ Csad 9.38E-05 2.23503XM_006515014 // Prkar2b // protein kinase, cAMP dependent regulatory, type II beta // 1 Prkar2b 1.62E-05 2.23581NM_025931 // Ift27 // intraflagellar transport 27 // 15|15 E2 // 67042 /// ENSMUST00000 Ift27 0.00139825 2.23637NM_146089 // Haus1 // HAUS augmin-like complex, subunit 1 // 18 E3|18 // 225745 /// XM_ Haus1 0.000164271 2.23693NM_001039185 // Ceacam1 // carcinoembryonic antigen-related cell adhesion molecule 1 // Ceacam1 0.000233652 2.23713NM_026005 // 2610301B20Rik // RIKEN cDNA 2610301B20 gene // 4 A1|4 // 67157 /// ENSMUST 2610301B20Rik 0.00108547 2.23766NM_010692 // Lbx2 // ladybird homeobox homolog 2 (Drosophila) // 6 C3|6 35.94 cM // 168 Lbx2 0.00016987 2.23937NM_011505 // Stxbp4 // syntaxin binding protein 4 // 11|11 C // 20913 /// XM_006532736 Stxbp4 0.000180973 2.23971--- 0.0015763 2.24038ENSMUST00000109020 // Gm14440 // predicted gene 14440 // 2|2 // 100503353 /// ENSMUST00 Gm14440 9.78E-07 2.2411NM_199446 // Phkb // phosphorylase kinase beta // 8 C3|8 41.61 cM // 102093 /// ENSMUST Phkb 2.61E-05 2.24127NM_016756 // Cdk2 // cyclin-dependent kinase 2 // 10 D3|10 // 12566 /// NM_183417 // Cd Cdk2 2.55E-05 2.24247NM_011121 // Plk1 // polo-like kinase 1 // 7 F3|7 65.52 cM // 18817 /// ENSMUST00000033 Plk1 7.55E-05 2.24465NM_001177406 // Gm14431 // predicted gene 14431 // 2|2 // 100303732 /// NM_001177407 // Gm14431 1.18E-06 2.24639NM_025914 // Actr6 // ARP6 actin-related protein 6 // 10 C2|10 // 67019 /// XM_00651396 Actr6 0.00324858 2.24656NM_172437 // Pus7l // pseudouridylate synthase 7 homolog (S. cerevisiae)-like // 15 E3| Pus7l 6.51E-05 2.24709NM_001289522 // Cad // carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, an Cad 4.72E-05 2.24733NM_145128 // Mgat5 // mannoside acetylglucosaminyltransferase 5 // 1 E3|1 // 107895 /// Mgat5 0.00205729 2.24777NM_001290986 // Wdr76 // WD repeat domain 76 // 2|2 F1 // 241627 /// NM_001290987 // Wd Wdr76 8.57E-05 2.2488NM_009104 // Rrm2 // ribonucleotide reductase M2 // 12 A1.3|12 8.5 cM // 20135 /// ENSM Rrm2 9.88E-07 2.25182NM_022331 // Herpud1 // homocysteine-inducible, endoplasmic reticulum stress-inducible, Herpud1 7.97E-07 2.25308NM_001163527 // Itpripl1 // inositol 1,4,5-triphosphate receptor interacting protein-li Itpripl1 2.88E-06 2.25314NM_001244692 // St18 // suppression of tumorigenicity 18 // 1 A1|1 // 240690 /// NM_001 St18 4.65E-07 2.25427NM_001164362 // Cep55 // centrosomal protein 55 // 19|19 C3 // 74107 /// NM_028293 // C Cep55 0.00227243 2.25454--- 0.000305216 2.25563NM_027891 // Lrwd1 // leucine-rich repeats and WD repeat domain containing 1 // 5 G2|5 Lrwd1 7.93E-05 2.25652NM_177036 // Ceacam19 // carcinoembryonic antigen-related cell adhesion molecule 19 // Ceacam19 0.000543992 2.25672NM_001109688 // C2cd5 // C2 calcium-dependent domain containing 5 // 6|6 G2 // 74741 // C2cd5 0.000105078 2.25881NR_045008 // Gm20300 // predicted gene, 20300 // 10|10 17.1 cM // 100504586 Gm20300 0.00145244 2.25893NM_009968 // Cryz // crystallin, zeta // 3 H4|3 // 12972 /// XM_006500973 // Cryz // cr Cryz 8.49E-05 2.2607NM_001113478 // Frrs1 // ferric-chelate reductase 1 // 3 G1|3 // 20321 /// NM_009146 // Frrs1 1.80E-08 2.26191ENSMUST00000067888 // Tpk1 // thiamine pyrophosphokinase // 6|6 B2 // 29807 /// NM_0138 Tpk1 0.00048912 2.26207NM_001111062 // Comt // catechol-O-methyltransferase // 16 A3|16 11.4 cM // 12846 /// N Comt 1.13E-05 2.26266NM_001253717 // Atg7 // autophagy related 7 // 6 E3|6 // 74244 /// NM_001253718 // Atg7 Atg7 2.74E-08 2.26323NM_011849 // Nek4 // NIMA (never in mitosis gene a)-related expressed kinase 4 // 14 B| Nek4 0.00126456 2.2635NM_178778 // Scai // suppressor of cancer cell invasion // 2 B|2 // 320271 /// ENSMUST0 Scai 3.46E-05 2.26379NM_008181 // Gsta1 // glutathione S-transferase, alpha 1 (Ya) // 9 E1|9 43.65 cM // 148 Gsta1 0.00481631 2.26492NM_026810 // Mlh1 // mutL homolog 1 (E. coli) // 9 F3|9 60.92 cM // 17350 /// XM_006511 Mlh1 0.000164756 2.26514ENSMUST00000140566 // Xxylt1 // xyloside xylosyltransferase 1 // 16 B2|16 // 268880 /// Xxylt1 0.000357804 2.26524ENSMUST00000057844 // B230219D22Rik // RIKEN cDNA B230219D22 gene // 13 B1|13 // 78521 B230219D22Rik 2.88E-07 2.26554NM_001167914 // Atxn3 // ataxin 3 // 12 E|12 // 110616 /// NM_029705 // Atxn3 // ataxin Atxn3 1.91E-05 2.26597NM_001081423 // Ttll5 // tubulin tyrosine ligase-like family, member 5 // 12|12 D3 // 3 Ttll5 0.000198579 2.26806NM_007422 // Adss // adenylosuccinate synthetase, non muscle // 1 H4|1 // 11566 /// XM_ Adss 1.80E-06 2.26896NR_015543 // 2810055G20Rik // RIKEN cDNA 2810055G20 gene // 16 C3.1|16 // 77994 /// ENS 2810055G20Rik 0.00491562 2.26921NM_025835 // Pccb // propionyl Coenzyme A carboxylase, beta polypeptide // 9 E4|9 // 66 Pccb 0.00188918 2.27037NM_008650 // Mut // methylmalonyl-Coenzyme A mutase // 17 C-D|17 19.55 cM // 17850 /// Mut 5.21E-06 2.27057XR_396594 // LOC102638208 // uncharacterized LOC102638208 // --- // 102638208 /// ENSMU LOC102638208 0.00287808 2.27074NM_001163643 // Map3k12 // mitogen-activated protein kinase kinase kinase 12 // 15 F3|1 Map3k12 0.000773391 2.27398NM_080446 // Helb // helicase (DNA) B // 10 D2|10 67.94 cM // 117599 /// ENSMUST0000002 Helb 5.16E-05 2.27445NM_172692 // Gba2 // glucosidase beta 2 // 4 B1|4 // 230101 /// ENSMUST00000030189 // G Gba2 8.60E-07 2.27532NM_009471 // Umps // uridine monophosphate synthetase // 16 B3|16 // 22247 /// XM_00652 Umps 7.67E-05 2.27596

NR_015572 // 1810014B01Rik // RIKEN cDNA 1810014B01 gene // 10|10 // 66263 /// ENSMUST0 1810014B01Rik 3.60E-05 2.28224NM_001085522 // Gm13251 // predicted gene 13251 // 4 E1|4 // 433791 /// ENSMUST00000105 Gm13251 0.000536732 2.28365NM_001290805 // Kif3a // kinesin family member 3A // 11 A5-B1|11 31.97 cM // 16568 /// Kif3a 1.28E-06 2.28391NM_028846 // Usp20 // ubiquitin specific peptidase 20 // 2 B|2 // 74270 /// XM_00649839 Usp20 0.000258428 2.28392NM_173047 // Cbr3 // carbonyl reductase 3 // 16 C4|16 54.58 cM // 109857 /// ENSMUST000 Cbr3 0.00146809 2.28395NM_001081158 // Cluh // clustered mitochondria (cluA/CLU1) homolog // 11 B4|11 // 74148 Cluh 6.62E-06 2.28398NR_045872 // Gm9054 // predicted gene 9054 // 3 F2.1|3 // 668224 Gm9054 0.000395323 2.2843NM_001082485 // Zfp266 // zinc finger protein 266 // 9 A3|9 // 77519 /// NM_001135019 / Zfp266 4.36E-06 2.28495NM_173400 // Haus6 // HAUS augmin-like complex, subunit 6 // 4 C4|4 40.69 cM // 230376 Haus6 0.00655314 2.28586NM_027903 // Dhdh // dihydrodiol dehydrogenase (dimeric) // 7 B2|7 29.32 cM // 71755 // Dhdh 2.51E-07 2.28611NM_172405 // Fam175a // family with sequence similarity 175, member A // 5 E4|5 // 7068 Fam175a 2.71E-06 2.28743NM_027185 // Def6 // differentially expressed in FDCP 6 // 17 A3.3|17 // 23853 /// ENSM Def6 0.00178009 2.28916NM_008512 // Lrp1 // low density lipoprotein receptor-related protein 1 // 10|10 B2-D1 Lrp1 9.87E-05 2.28942NM_134420 // Slc26a6 // solute carrier family 26, member 6 // 9 F2|9 // 171429 /// ENSM Slc26a6 2.31E-06 2.29087--- 0.00112324 2.29121XR_387513 // 6230416C02Rik // RIKEN cDNA 6230416C02 gene // 2 H4|2 // 545490 /// NM_001 6230416C02Rik 2.00E-07 2.29133NM_007988 // Fasn // fatty acid synthase // 11 E2|11 84.56 cM // 14104 /// ENSMUST00000 Fasn 6.13E-07 2.29201NM_018869 // Grk5 // G protein-coupled receptor kinase 5 // 19 D3|19 56.52 cM // 14773 Grk5 8.15E-05 2.29278NM_053119 // Echs1 // enoyl Coenzyme A hydratase, short chain, 1, mitochondrial // 7 F4 Echs1 2.11E-05 2.29284ENSMUST00000139492 // Gm13710 // predicted gene 13710 // 2 D|2 // 672763 Gm13710 0.00256092 2.29337NM_001165253 // Ctage5 // CTAGE family, member 5 // 12 C1|12 26.01 cM // 217615 /// NM_ Ctage5 1.73E-06 2.29345NM_028820 // 1700017B05Rik // RIKEN cDNA 1700017B05 gene // 9 C|9 30.89 cM // 74211 /// 1700017B05Rik 7.95E-05 2.29361NM_019484 // Alyref2 // Aly/REF export factor 2 // 1 H3|1 // 56009 /// ENSMUST000000815 Alyref2 0.00232703 2.29367--- 4.36E-05 2.29372ENSMUST00000014892 // Tex261 // testis expressed gene 261 // 6 C3|6 35.94 cM // 21766 / Tex261 1.96E-05 2.29376NM_145928 // Tspan14 // tetraspanin 14 // 14 B|14 22.36 cM // 52588 /// XM_006519261 // Tspan14 2.05E-05 2.29629NM_010441 // Hmga2 // high mobility group AT-hook 2 // 10 D2|10 67.94 cM // 15364 /// E Hmga2 0.000474527 2.29662NM_029631 // Abhd14b // abhydrolase domain containing 14b // 9 F1|9 // 76491 /// XM_006 Abhd14b 0.000620664 2.29871NM_001033294 // Ddx31 // DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 31 // 2 A3|2 // 2 Ddx31 0.00155558 2.3028NM_138587 // Fam3c // family with sequence similarity 3, member C // 6 A3.1|6 9.24 cM / Fam3c 1.56E-05 2.30303NM_001159369 // Polq // polymerase (DNA directed), theta // 16 B3|16 26.32 cM // 77782 Polq 0.000145124 2.30394ENSMUST00000180820 // C630016N16Rik // RIKEN cDNA C630016N16 gene // 7 B1|7 // 791088 / C630016N16Rik 0.000112169 2.30492--- 0.000102613 2.30533NM_001163073 // Lcorl // ligand dependent nuclear receptor corepressor-like // 5 B3|5 / Lcorl 4.76E-06 2.30645NM_001290662 // Kif2c // kinesin family member 2C // 4 D1|4 53.42 cM // 73804 /// NM_13 Kif2c 7.19E-05 2.30651NM_011948 // Map3k4 // mitogen-activated protein kinase kinase kinase 4 // 17 A1|17 8.4 Map3k4 3.43E-05 2.30714NM_178798 // Slc7a6 // solute carrier family 7 (cationic amino acid transporter, y+ sys Slc7a6 1.65E-06 2.3077NM_147220 // Abca9 // ATP-binding cassette, sub-family A (ABC1), member 9 // 11 E1|11 / Abca9 1.54E-05 2.30829NM_198292 // Tex2 // testis expressed gene 2 // 11 D|11 69.46 cM // 21763 /// XM_006533 Tex2 2.04E-05 2.30853NM_001081189 // Uprt // uracil phosphoribosyltransferase (FUR1) homolog (S. cerevisiae) Uprt 4.28E-06 2.30888NM_011391 // Slc16a7 // solute carrier family 16 (monocarboxylic acid transporters), me Slc16a7 1.26E-06 2.31025NM_001081353 // 2210408I21Rik // RIKEN cDNA 2210408I21 gene // 13 C1|13 // 72371 /// NM 2210408I21Rik 4.08E-05 2.31032NM_139303 // Kif18a // kinesin family member 18A // 2 E3|2 // 228421 /// ENSMUST0000002 Kif18a 0.00253734 2.31148NM_001081098 // Zfp362 // zinc finger protein 362 // 4 D2.2|4 // 230761 /// ENSMUST0000 Zfp362 7.31E-06 2.31203--- 1.73E-05 2.31336NM_176979 // Topbp1 // topoisomerase (DNA) II binding protein 1 // 9 F1|9 // 235559 /// Topbp1 2.23E-05 2.31381ENSMUST00000109020 // Gm14440 // predicted gene 14440 // 2|2 // 100503353 /// ENSMUST00 Gm14440 7.80E-08 2.31435NM_175360 // Obfc1 // oligonucleotide/oligosaccharide-binding fold containing 1 // 19 D Obfc1 1.45E-05 2.31551NM_029249 // Parpbp // PARP1 binding protein // 10 C2|10 // 75317 /// ENSMUST0000004851 Parpbp 0.00166508 2.31611NM_023737 // Ehhadh // enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogena Ehhadh 0.000196923 2.31705NM_080795 // Lnx2 // ligand of numb-protein X 2 // 5|5 G2 // 140887 /// ENSMUST00000016 Lnx2 9.94E-05 2.32117NM_173450 // Rpusd2 // RNA pseudouridylate synthase domain containing 2 // 2 E5|2 // 27 Rpusd2 2.84E-05 2.32134ENSMUST00000180951 // D130017N08Rik // RIKEN cDNA D130017N08 gene // 5 G2|5 // 320064 / D130017N08Rik 5.66E-05 2.32259XR_387077 // Ap1s2 // adaptor-related protein complex 1, sigma 2 subunit // X F5|X // 1 Ap1s2 1.88E-06 2.32308NM_080462 // Hnmt // histamine N-methyltransferase // 2 A3|2 // 140483 /// XM_006497671 Hnmt 6.89E-05 2.32459NM_199447 // Rrp12 // ribosomal RNA processing 12 homolog (S. cerevisiae) // 19 C3|19 / Rrp12 0.000151591 2.32462NM_019665 // Arl6 // ADP-ribosylation factor-like 6 // 16|16 C1.2 // 56297 /// ENSMUST0 Arl6 6.56E-05 2.32651NM_009730 // Atrn // attractin // 2 F1|2 63.26 cM // 11990 /// ENSMUST00000028781 // At Atrn 1.80E-06 2.32683NM_001111017 // Serac1 // serine active site containing 1 // 17 A1|17 3.67 cM // 321007 Serac1 8.76E-07 2.32761NM_001122989 // Cdc14b // CDC14 cell division cycle 14B // 13 B3|13 // 218294 /// NM_17 Cdc14b 0.000104877 2.3279NM_174848 // Crybg3 // beta-gamma crystallin domain containing 3 // 16 C1.3|16 // 22427 Crybg3 1.30E-06 2.32883NM_027895 // Ulk3 // unc-51-like kinase 3 // 9|9 C // 71742 /// XR_379456 // Ulk3 // un Ulk3 0.00357633 2.32964NM_001127351 // Sirt3 // sirtuin 3 // 7|7 F4 // 64384 /// NM_001177804 // Sirt3 // sirt Sirt3 0.00270536 2.33062NM_025522 // Dhrs7 // dehydrogenase/reductase (SDR family) member 7 // 12 C3|12 // 6637 Dhrs7 4.73E-06 2.33159NM_001013256 // Ctc1 // CTS telomere maintenance complex component 1 // 11 B3|11 // 689 Ctc1 1.15E-06 2.33176NM_011779 // Coro1c // coronin, actin binding protein 1C // 5 F|5 // 23790 /// ENSMUST0 Coro1c 7.84E-08 2.33396XM_006522459 // Cmss1 // cms small ribosomal subunit 1 // 16 C1.1|16 // 66497 /// XM_00 Cmss1 0.00170036 2.33577NM_177780 // Dock5 // dedicator of cytokinesis 5 // 14 D1|14 // 68813 /// ENSMUST000000 Dock5 2.66E-07 2.33621NM_011467 // Spr // sepiapterin reductase // 6 C3|6 37.15 cM // 20751 /// ENSMUST000000 Spr 0.00195049 2.33659--- 0.00104491 2.33702NM_028335 // Zfp248 // zinc finger protein 248 // 6 F1|6 // 72720 /// XM_006506676 // Z Zfp248 0.000105512 2.34052NM_146151 // Tesk2 // testis-specific kinase 2 // 4 D1|4 // 230661 /// ENSMUST000000455 Tesk2 0.00112008 2.34284ENSMUST00000120593 // Bcl7a // B cell CLL/lymphoma 7A // 5 F|5 // 77045 /// NM_029850 / Bcl7a 0.000225122 2.34351NM_001025586 // Nr2c2ap // nuclear receptor 2C2-associated protein // 8 B3.3|8 // 75692 Nr2c2ap 0.00313757 2.34387NM_009547 // Zbtb14 // zinc finger and BTB domain containing 14 // 17 E1.3|17 40.42 cM Zbtb14 0.00010163 2.34402ENSMUST00000180411 // Gm17491 // predicted gene, 17491 // 8|8 11.42 cM // 100502938 Gm17491 2.23E-05 2.34421NM_001040395 // Nadk2 // NAD kinase 2, mitochondrial // 15|15 A2 // 68646 /// NM_001085 Nadk2 3.34E-05 2.3445NM_001294322 // Mpv17 // MpV17 mitochondrial inner membrane protein // 5 B1|5 // 17527 Mpv17 7.81E-06 2.34507--- 0.00500611 2.3468--- 0.00500611 2.3468NM_009560 // Zfp60 // zinc finger protein 60 // 7 A3|7 15.97 cM // 22718 /// ENSMUST000 Zfp60 0.00465339 2.34706ENSMUST00000181295 // Gm26895 // predicted gene, 26895 // --- // --- Gm26895 0.000916429 2.34733NM_028276 // Utp14a // UTP14, U3 small nucleolar ribonucleoprotein, homolog A (yeast) / Utp14a 2.21E-07 2.34771NM_001198785 // Aatk // apoptosis-associated tyrosine kinase // 11 E2|11 // 11302 /// N Aatk 0.000232864 2.34957NM_007382 // Acadm // acyl-Coenzyme A dehydrogenase, medium chain // 3 H3|3 78.77 cM // Acadm 7.84E-07 2.35006NM_001037955 // Dusp22 // dual specificity phosphatase 22 // 13 A3.2|13 // 105352 /// N Dusp22 5.56E-07 2.35016NM_133947 // Numa1 // nuclear mitotic apparatus protein 1 // 7 E3|7 // 101706 /// XM_00 Numa1 1.99E-05 2.35121NM_198305 // Klhl17 // kelch-like 17 // 4 E2|4 // 231003 /// ENSMUST00000105569 // Klhl Klhl17 0.000192269 2.35236NM_173347 // Prune // prune homolog (Drosophila) // 3 F2.1|3 // 229589 /// ENSMUST00000 Prune 1.53E-05 2.35267NM_153126 // Nat10 // N-acetyltransferase 10 // 2 E2|2 // 98956 /// XM_006500455 // Nat Nat10 4.12E-05 2.35358NM_008855 // Prkcb // protein kinase C, beta // 7 F3|7 65.75 cM // 18751 /// ENSMUST000 Prkcb 1.24E-06 2.35358NM_175158 // Utp20 // UTP20, small subunit (SSU) processome component, homolog (yeast) Utp20 6.71E-06 2.35402NM_181417 // Csrp2bp // cysteine and glycine-rich protein 2 binding protein // 2 G1|2 7 Csrp2bp 0.000275039 2.35767

NM_023166 // Fam89b // family with sequence similarity 89, member B // 19 A|19 4.34 cM Fam89b 3.60E-05 2.36007ENSMUST00000182761 // Gm20204 // predicted gene, 20204 // --- // --- Gm20204 0.00132864 2.36031--- 0.00040221 2.36141NR_002900 // Snora69 // small nucleolar RNA, H/ACA box 69 // X A3.3|X // 104369 /// ENS Snora69 0.00533264 2.36148NM_007564 // Zfp36l1 // zinc finger protein 36, C3H type-like 1 // 12 C3|12 // 12192 // Zfp36l1 2.73E-05 2.3619ENSMUST00000124845 // Sgsm3 // small G protein signaling modulator 3 // 15 E1|15 // 105 Sgsm3 0.00147725 2.36209NM_029321 // Ttc32 // tetratricopeptide repeat domain 32 // 12|12 A1.3 // 75516 /// ENS Ttc32 0.000236685 2.36215NM_008964 // Ptger2 // prostaglandin E receptor 2 (subtype EP2) // 14 C1|14 22.68 cM // Ptger2 2.50E-05 2.36313NM_153104 // Phospho1 // phosphatase, orphan 1 // 11 D|11 59.01 cM // 237928 /// ENSMUS Phospho1 0.00320414 2.36388AK144456 // Gm19703 // predicted gene, 19703 // 14|14 22.36 cM // 100503457 Gm19703 0.0064732 2.36518NM_001289429 // Cipc // CLOCK interacting protein, circadian // 12 D2|12 // 217732 /// Cipc 6.13E-07 2.36519ENSMUST00000075558 // Hist2h3b // histone cluster 2, H3b // 3 F2.1|3 // 319154 /// ENSM Hist2h3b 0.00618477 2.3654NM_175534 // Mrgpre // MAS-related GPR, member E // 7 F5|7 // 244238 /// ENSMUST0000005 Mrgpre 0.000394503 2.36652NM_007520 // Bach1 // BTB and CNC homology 1 // 16 C3.3|16 // 12013 /// ENSMUST00000026 Bach1 6.35E-08 2.36717NM_001205241 // Kat6b // K(lysine) acetyltransferase 6B // 14 A3|14 // 54169 /// NM_017 Kat6b 0.000431291 2.36782NR_028281 // Snord43 // small nucleolar RNA, C/D box 43 // 15 E1|15 // 100302600 Snord43 0.00552183 2.36849NM_001170333 // Clec4a2 // C-type lectin domain family 4, member a2 // 6 F3|6 58.18 cM Clec4a2 0.000272358 2.36893NM_001113486 // Sept9 // septin 9 // 11 E2|11 82.61 cM // 53860 /// NM_001113488 // Sep Sep-09 4.32E-08 2.36911NM_198411 // Inf2 // inverted formin, FH2 and WH2 domain containing // 12 F1|12 // 7043 Inf2 0.000582474 2.36936--- 0.00623899 2.36961NM_029861 // Cnrip1 // cannabinoid receptor interacting protein 1 // 11|11 A3.1 // 3806 Cnrip1 0.000800361 2.37027NM_134054 // Sptssa // serine palmitoyltransferase, small subunit A // 12 C1|12 // 1047 Sptssa 0.000782767 2.37034NM_144558 // Bivm // basic, immunoglobulin-like variable motif containing // 1 C1.1|1 / Bivm 2.52E-05 2.37073NM_001271397 // Nol8 // nucleolar protein 8 // 13 B1|13 25.36 cM // 70930 /// NR_073167 Nol8 7.14E-07 2.37104ENSMUST00000101077 // A530017D24Rik // RIKEN cDNA A530017D24 gene // --- // --- /// ENS A530017D24Rik 6.88E-05 2.37112NM_028758 // Gga2 // golgi associated, gamma adaptin ear containing, ARF binding protei Gga2 1.76E-05 2.37121NM_009898 // Coro1a // coronin, actin binding protein 1A // 7 F3|7 69.25 cM // 12721 // Coro1a 4.35E-06 2.37168NM_001163622 // Prepl // prolyl endopeptidase-like // 17 E4|17 // 213760 /// NM_0011636 Prepl 4.53E-06 2.37244NM_028761 // Parn // poly(A)-specific ribonuclease (deadenylation nuclease) // 16|16 B1 Parn 0.0017242 2.37254NM_001024604 // Ankrd28 // ankyrin repeat domain 28 // 14 B|14 // 105522 /// ENSMUST000 Ankrd28 1.37E-05 2.37279XR_404983 // LOC102635305 // uncharacterized LOC102635305 // --- // 102635305 /// ENSMU LOC102635305 0.000247763 2.37281NM_025294 // Natd1 // N-acetyltransferase domain containing 1 // 11 B2|11 // 24083 /// Natd1 1.76E-05 2.37658NM_133943 // Hsd3b7 // hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta Hsd3b7 8.20E-05 2.37796--- 0.00330554 2.37827NM_026812 // Hddc3 // HD domain containing 3 // 7 D3|7 // 68695 /// ENSMUST00000032747 Hddc3 0.000264677 2.37884--- 0.00132548 2.38109NM_146108 // Hibch // 3-hydroxyisobutyryl-Coenzyme A hydrolase // 1 C1.1|1 // 227095 // Hibch 0.000730385 2.38175NM_010124 // Eif4ebp2 // eukaryotic translation initiation factor 4E binding protein 2 Eif4ebp2 0.000130281 2.38192NM_152822 // Las1l // LAS1-like (S. cerevisiae) // X C3|X // 76130 /// ENSMUST000000799 Las1l 8.05E-06 2.38193NM_009228 // Snta1 // syntrophin, acidic 1 // 2 H1|2 76.52 cM // 20648 /// ENSMUST00000 Snta1 8.06E-05 2.38226NM_030715 // Polh // polymerase (DNA directed), eta (RAD 30 related) // 17|17 C // 8090 Polh 0.00234791 2.38343NM_001083334 // Bin1 // bridging integrator 1 // 18 B1|18 18.01 cM // 30948 /// NM_0096 Bin1 7.67E-07 2.38403NM_001177406 // Gm14431 // predicted gene 14431 // 2|2 // 100303732 /// NM_001177407 // Gm14431 5.48E-07 2.38446ENSMUST00000122924 // Nudt8 // nudix (nucleoside diphosphate linked moiety X)-type moti Nudt8 0.00390209 2.38577NM_021356 // Gab1 // growth factor receptor bound protein 2-associated protein 1 // 8 C Gab1 7.10E-07 2.38641NM_021555 // Fam203a // family with sequence similarity 203, member A // 15 D3|15 35.78 Fam203a 0.00271615 2.38745NM_008795 // Cdk18 // cyclin-dependent kinase 18 // 1 E4|1 // 18557 /// XR_387152 // Cd Cdk18 7.18E-09 2.38796NM_001289666 // Tmem241 // transmembrane protein 241 // 18 A1|18 // 338363 /// NM_00128 Tmem241 8.14E-06 2.39084NM_001081368 // Tbccd1 // TBCC domain containing 1 // 16 B1|16 // 70573 /// XM_00652256 Tbccd1 1.54E-05 2.39091--- 0.00427787 2.39158NM_027560 // Arrdc2 // arrestin domain containing 2 // 8|8 C1 // 70807 /// ENSMUST00000 Arrdc2 0.000635508 2.39195NM_182995 // Ccp110 // centriolar coiled coil protein 110 // 7 F2|7 // 101565 /// ENSMU Ccp110 8.57E-05 2.39256NM_021392 // Ap4m1 // adaptor-related protein complex AP-4, mu 1 // 5|5 G1 // 11781 /// Ap4m1 5.31E-06 2.39292NM_029148 // Tmx4 // thioredoxin-related transmembrane protein 4 // 2 G1|2 65.66 cM // Tmx4 8.26E-05 2.39439NM_199033 // Tsen2 // tRNA splicing endonuclease 2 homolog (S. cerevisiae) // 6 E3|6 // Tsen2 0.00496094 2.39536NM_023284 // Nuf2 // NUF2, NDC80 kinetochore complex component, homolog (S. cerevisiae) Nuf2 0.000353768 2.39599NM_178664 // B3gntl1 // UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase-lik B3gntl1 0.000215719 2.39612NM_153780 // 2610044O15Rik8 // RIKEN cDNA 2610044O15 gene // 8 E2|8 // 72139 /// BC0238 2610044O15Rik 0.00325599 2.39683NR_030670 // Gm15760 // mitochondrial ribosomal protein S18B pseudogene // 16 A3|16 // Gm15760 1.45E-05 2.39695NM_001205236 // Arhgap27 // Rho GTPase activating protein 27 // 11 E1|11 // 544817 /// Arhgap27 0.000112681 2.4001NM_001128094 // Atp13a3 // ATPase type 13A3 // 16 B2|16 // 224088 /// NM_001128096 // A Atp13a3 1.33E-06 2.40094NM_008017 // Smc2 // structural maintenance of chromosomes 2 // 4 B3|4 28.31 cM // 1421 Smc2 3.65E-05 2.40149NM_181541 // Caprin2 // caprin family member 2 // 6 G3|6 // 232560 /// ENSMUST000000723 Caprin2 0.000738078 2.4021AK144475 // Nr2f6 // nuclear receptor subfamily 2, group F, member 6 // 8 B3.3|8 34.43 Nr2f6 0.00263242 2.40252NM_153560 // Fam102a // family with sequence similarity 102, member A // 2 B|2 // 98952 Fam102a 4.49E-05 2.40261NM_026174 // Entpd4 // ectonucleoside triphosphate diphosphohydrolase 4 // 14 D2|14 // Entpd4 2.62E-09 2.40262NM_175212 // Tmem65 // transmembrane protein 65 // 15 D1|15 // 74868 /// ENSMUST0000007 Tmem65 1.23E-06 2.40313NM_144815 // Cecr5 // cat eye syndrome chromosome region, candidate 5 // 6 F1|6 56.95 c Cecr5 0.00126825 2.40316NM_028792 // Josd1 // Josephin domain containing 1 // 15 E1|15 // 74158 /// XM_00148098 Josd1 3.57E-05 2.40351NM_177353 // Slc9a7 // solute carrier family 9 (sodium/hydrogen exchanger), member 7 // Slc9a7 2.98E-05 2.40606--- 0.00606163 2.40697NM_001145898 // BC052040 // cDNA sequence BC052040 // 2 E4|2 // 399568 /// NM_207264 // BC052040 0.00130537 2.40739XM_006534256 // Coasy // Coenzyme A synthase // 11 D|11 // 71743 /// ENSMUST00000001806 Coasy 8.15E-05 2.40791NM_009211 // Smarcc1 // SWI/SNF related, matrix associated, actin dependent regulator o Smarcc1 0.000264712 2.40896NM_019933 // Ptpn4 // protein tyrosine phosphatase, non-receptor type 4 // 1 E2|1 52.39 Ptpn4 3.80E-05 2.40931NM_019455 // Hpgds // hematopoietic prostaglandin D synthase // 6|6 D-E // 54486 /// EN Hpgds 7.67E-06 2.41003NM_019864 // Atr // ataxia telangiectasia and Rad3 related // 9 E4|9 // 245000 /// ENSM Atr 0.000248518 2.41046NM_172289 // Slc36a4 // solute carrier family 36 (proton/amino acid symporter), member Slc36a4 6.18E-06 2.41236NM_010244 // Fv1 // Friend virus susceptibility 1 // 4 E2|4 78.56 cM // 14349 /// ENSMU Fv1 0.00296833 2.41275NM_001163421 // Tatdn3 // TatD DNase domain containing 3 // 1 H6|1 // 68972 /// NM_0011 Tatdn3 1.52E-05 2.41306NM_001014974 // Ttll4 // tubulin tyrosine ligase-like family, member 4 // 1 C3|1 // 675 Ttll4 0.0020628 2.4133AK134193 // Gm19313 // predicted gene, 19313 // 4 E2|4 86.17 cM // 100502668 Gm19313 0.000385729 2.4137NM_013454 // Abca1 // ATP-binding cassette, sub-family A (ABC1), member 1 // 4 A5-B3|4 Abca1 1.00E-09 2.41396NM_025957 // Ceacam14 // carcinoembryonic antigen-related cell adhesion molecule 14 // Ceacam14 0.00373775 2.4145NM_011762 // Zfp59 // zinc finger protein 59 // 7 A3|7 // 22717 /// XM_006539744 // Zfp Zfp59 1.01E-05 2.41459NM_025377 // Ska2 // spindle and kinetochore associated complex subunit 2 // 11 C|11 // Ska2 0.000343914 2.41818NM_015818 // Hs6st1 // heparan sulfate 6-O-sulfotransferase 1 // 1 B|1 // 50785 /// ENS Hs6st1 0.000440687 2.42001NM_145960 // Mtrf1 // mitochondrial translational release factor 1 // 14 D3|14 // 21125 Mtrf1 0.00109378 2.42115NM_178162 // Agfg2 // ArfGAP with FG repeats 2 // 5 G2|5 // 231801 /// XM_006504567 // Agfg2 5.19E-06 2.42285NM_028428 // Fut11 // fucosyltransferase 11 // 14|14 B // 73068 /// ENSMUST00000048016 Fut11 1.24E-06 2.42594ENSMUST00000131743 // Polr2e // polymerase (RNA) II (DNA directed) polypeptide E // 10 Polr2e 1.23E-06 2.4275NM_001042527 // Blm // Bloom syndrome, RecQ helicase-like // 7 D3|7 45.65 cM // 12144 / Blm 8.32E-05 2.42928NM_181584 // Gab3 // growth factor receptor bound protein 2-associated protein 3 // X A Gab3 0.000283164 2.4294

NM_010302 // Gna12 // guanine nucleotide binding protein, alpha 12 // 5 G2|5 79.3 cM // Gna12 4.50E-07 2.42949NM_172371 // Slc16a13 // solute carrier family 16 (monocarboxylic acid transporters), m Slc16a13 3.90E-05 2.4327XR_382919 // LOC102636620 // uncharacterized LOC102636620 // --- // 102636620 /// ENSMU LOC102636620 0.000337138 2.43277--- 0.0019873 2.43463ENSMUST00000110934 // Cnpy4 // canopy 4 homolog (zebrafish) // 5 G2|5 // 66455 /// BC09 Cnpy4 2.41E-05 2.43469NM_026891 // Cdan1 // congenital dyserythropoietic anemia, type I (human) // 2 E5|2 // Cdan1 1.61E-05 2.43504NM_175429 // Kctd12b // potassium channel tetramerisation domain containing 12b // X F3 Kctd12b 2.71E-05 2.43596NM_001165256 // Dcaf4 // DDB1 and CUL4 associated factor 4 // 12|12 D3 // 73828 /// NM_ Dcaf4 1.88E-05 2.43656NM_029665 // Ipo11 // importin 11 // 13 D2.1|13 // 76582 /// XR_382746 // Ipo11 // impo Ipo11 9.01E-05 2.44157--- 0.00196459 2.44286NM_026283 // Samd8 // sterile alpha motif domain containing 8 // 14|14 B // 67630 /// X Samd8 0.000121553 2.44395--- 0.000899052 2.44471NM_138753 // Hexim1 // hexamethylene bis-acetamide inducible 1 // 11 E1|11 // 192231 // Hexim1 5.33E-06 2.44516NM_016845 // Acrbp // proacrosin binding protein // 6|6 F2 // 54137 /// NM_001127340 // Acrbp 9.17E-05 2.44516--- 0.000454592 2.44601NM_027477 // Zfp398 // zinc finger protein 398 // 6|6 B3 // 272347 /// NM_173034 // Zfp Zfp398 0.0049031 2.4473NM_053214 // Myo1f // myosin IF // 17 B-C|17 17.98 cM // 17916 /// ENSMUST00000087605 / Myo1f 4.92E-06 2.44827NM_025578 // Mrps25 // mitochondrial ribosomal protein S25 // 6|6 D3 // 64658 /// ENSMU Mrps25 0.00543108 2.45216NM_153083 // Thtpa // thiamine triphosphatase // 14 C1|14 // 105663 /// ENSMUST00000050 Thtpa 0.00021016 2.45217NM_010559 // Il6ra // interleukin 6 receptor, alpha // 3 F1|3 39.19 cM // 16194 /// ENS Il6ra 2.30E-07 2.45231NM_001205353 // Gramd4 // GRAM domain containing 4 // 15 E2|15 // 223752 /// NM_172611 Gramd4 0.000145638 2.45262XM_006514220 // Tmem198b // transmembrane protein 198b // 10 D3|10 // 73827 /// XM_0065 Tmem198b 0.00014918 2.45274NM_145612 // Zfp810 // zinc finger protein 810 // 9 A3|9 // 235050 /// ENSMUST000000862 Zfp810 0.000335069 2.45301NM_001146199 // Ptpn21 // protein tyrosine phosphatase, non-receptor type 21 // 12|12 F Ptpn21 0.000157261 2.4537NM_029037 // Pomk // protein-O-mannose kinase // 8|8 A3 // 74653 /// ENSMUST00000061850 Pomk 0.000365969 2.45792NM_001146153 // Homer3 // homer homolog 3 (Drosophila) // 8|8 C1 // 26558 /// NM_011984 Homer3 0.000405092 2.45951--- 5.90E-08 2.45981NM_001159907 // Gm17296 // predicted gene, 17296 // 8 E2|8 // 212728 /// XM_006530818 / Gm17296 0.00320063 2.46235NM_026539 // Chd1l // chromodomain helicase DNA binding protein 1-like // 3|3 F2 // 680 Chd1l 8.72E-06 2.46357--- 0.000550353 2.46388NM_013630 // Pkd1 // polycystic kidney disease 1 homolog // 17 A3.3|17 12.4 cM // 18763 Pkd1 6.34E-05 2.4646NM_028065 // Cnpy3 // canopy 3 homolog (zebrafish) // 17|17 C // 72029 /// ENSMUST00000 Cnpy3 1.43E-05 2.46461NM_019551 // Tdp2 // tyrosyl-DNA phosphodiesterase 2 // 13 A3.1|13 10.7 cM // 56196 /// Tdp2 0.000896154 2.46637ENSMUST00000166047 // Gm17122 // predicted gene 17122 // --- // --- /// AK188192 // Cor Gm17122 3.48E-05 2.46655NM_010424 // Hfe // hemochromatosis // 13 A2-A4|13 9.88 cM // 15216 /// XM_006516556 // Hfe 2.48E-05 2.46719NM_138607 // Fam50a // family with sequence similarity 50, member A // X A7.3|X // 1081 Fam50a 8.73E-06 2.46738NR_045266 // Gm15545 // predicted gene 15545 // 7|7 29.07 cM // 100502630 /// ENSMUST00 Gm15545 0.00297772 2.47112NM_172280 // 2210018M11Rik // RIKEN cDNA 2210018M11 gene // 7 E2|7 // 233545 /// XR_378 2210018M11Ri 7.71E-06 2.47311NM_001113550 // 4833420G17Rik // RIKEN cDNA 4833420G17 gene // 13 D2.3|13 // 67392 /// 4833420G17Rik 2.95E-06 2.4732NM_007760 // Crat // carnitine acetyltransferase // 2 B|2 21.69 cM // 12908 /// ENSMUST Crat 3.17E-06 2.47341NM_183195 // Marveld1 // MARVEL (membrane-associating) domain containing 1 // 19 C3|19 Marveld1 0.000148247 2.47347NM_007421 // Adssl1 // adenylosuccinate synthetase like 1 // 12 F1|12 // 11565 /// ENSM Adssl1 5.98E-07 2.47535NM_023397 // Mdp1 // magnesium-dependent phosphatase 1 // 14 C3|14 // 67881 /// NR_0283 Mdp1 7.14E-05 2.47638XR_401827 // LOC102643030 // uncharacterized LOC102643030 // --- // 102643030 /// XR_40 LOC102643030 0.00629546 2.47673NM_011273 // Xpr1 // xenotropic and polytropic retrovirus receptor 1 // 1 G3|1 66.49 cM Xpr1 1.91E-07 2.47696NM_025412 // Pycrl // pyrroline-5-carboxylate reductase-like // 15|15 E1 // 66194 /// X Pycrl 0.00324916 2.47756NM_026160 // Map1lc3b // microtubule-associated protein 1 light chain 3 beta // 8 E1|8 Map1lc3b 5.65E-05 2.47789NM_001163847 // Tbc1d24 // TBC1 domain family, member 24 // 17 A3.3|17 // 224617 /// NM Tbc1d24 0.00250299 2.47828NM_026674 // Aph1c // anterior pharynx defective 1c homolog (C. elegans) // 9 C|9 // 68 Aph1c 8.54E-06 2.47925NM_026319 // Ift74 // intraflagellar transport 74 // 4 C5|4 // 67694 /// XM_006503324 / Ift74 1.08E-06 2.47988NM_029394 // Snx24 // sorting nexing 24 // 18 D1|18 // 69226 /// XM_006526220 // Snx24 Snx24 1.73E-06 2.4833NM_001270495 // Tmem254b // transmembrane protein 254b // 14 A3|14 // 100039257 /// NM_ Tmem254b 0.000190748 2.48407NM_001163640 // Chn2 // chimerin 2 // 6 B3|6 // 69993 /// NM_023543 // Chn2 // chimerin Chn2 0.000358745 2.48463NM_010957 // Ogg1 // 8-oxoguanine DNA-glycosylase 1 // 6 E-F1|6 52.75 cM // 18294 /// E Ogg1 8.35E-06 2.48542NM_025556 // Coprs // coordinator of PRMT5, differentiation stimulator // 8 A1.1|8 // 6 Coprs 0.000455255 2.48558NM_001205068 // Jmjd4 // jumonji domain containing 4 // 11 B1.3|11 // 194952 /// NM_178 Jmjd4 0.0010577 2.48663NM_001252573 // Slc35c2 // solute carrier family 35, member C2 // 2 H3|2 85.53 cM // 22 Slc35c2 0.000370199 2.49205NM_133706 // Tmem97 // transmembrane protein 97 // 11 B5|11 46.74 cM // 69071 /// ENSMU Tmem97 0.000225917 2.49221NM_198033 // Setx // senataxin // 2 A3|2 // 269254 /// ENSMUST00000061578 // Setx // se Setx 4.68E-06 2.49244NM_199301 // Mtg1 // mitochondrial GTPase 1 homolog (S. cerevisiae) // 7 F4|7 // 212508 Mtg1 0.00145106 2.49625NM_172903 // Man2a2 // mannosidase 2, alpha 2 // 7 D2|7 // 140481 /// ENSMUST0000009834 Man2a2 7.81E-08 2.49761--- 0.00627641 2.50042NM_178364 // Zfp369 // zinc finger protein 369 // 13 B3|13 // 170936 /// ENSMUST0000012 Zfp369 0.000128323 2.50182NM_145425 // Wdpcp // WD repeat containing planar cell polarity effector // 11 A3.1|11 Wdpcp 0.00272914 2.5032NM_001161111 // Pqlc3 // PQ loop repeat containing // 12 A1.1|12 // 217430 /// NM_17257 Pqlc3 4.58E-08 2.50356NM_001162416 // Pfkfb2 // 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 // 1 E4 Pfkfb2 3.51E-05 2.5051--- 0.000725877 2.50568NM_133738 // Antxr2 // anthrax toxin receptor 2 // 5 E3|5 // 71914 /// ENSMUST000000312 Antxr2 3.66E-06 2.50676ENSMUST00000169406 // Gm1818 // predicted gene 1818 // 12 B3|12 // 217536 /// M74555 // Gm1818 0.000285459 2.50919NM_024229 // Pcyt2 // phosphate cytidylyltransferase 2, ethanolamine // 11 E2|11 // 686 Pcyt2 5.55E-05 2.51029NM_013881 // Ulk2 // unc-51 like kinase 2 // 11 B2|11 // 29869 /// XM_006533508 // Ulk2 Ulk2 1.10E-05 2.51468NM_008279 // Map4k1 // mitogen-activated protein kinase kinase kinase kinase 1 // 7 B1| Map4k1 1.22E-06 2.51493NM_008494 // Lfng // LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase // 5 Lfng 4.29E-06 2.51572NM_001270495 // Tmem254b // transmembrane protein 254b // 14 A3|14 // 100039257 /// NM_ Tmem254b 0.00052874 2.51587NM_001033142 // Rnf166 // ring finger protein 166 // 8 E1|8 // 68718 /// XM_006531336 / Rnf166 3.30E-05 2.5164NM_010813 // Mnt // max binding protein // 11 B-C|11 45.76 cM // 17428 /// XM_006532403 Mnt 0.000186951 2.51664NR_033628 // AA474331 // expressed sequence AA474331 // 10 B1|10 // 213332 /// ENSMUST0 AA474331 0.000709409 2.51671NM_001127330 // Pparg // peroxisome proliferator activated receptor gamma // 6 E3-F1|6 Pparg 4.02E-07 2.51843NM_001033872 // Smagp // small cell adhesion glycoprotein // 15 F1|15 // 207818 /// NM_ Smagp 0.000317397 2.51906NM_178620 // Mfsd11 // major facilitator superfamily domain containing 11 // 11 E2|11 / Mfsd11 1.09E-06 2.52018NM_145456 // Zswim6 // zinc finger SWIM-type containing 6 // 13 D2.1|13 // 67263 /// EN Zswim6 1.34E-05 2.5226NM_001081152 // Npat // nuclear protein in the AT region // 9 A5.3|9 29.12 cM // 244879 Npat 7.36E-06 2.52364--- 0.00313702 2.52399NM_001199060 // Wdr12 // WD repeat domain 12 // 1|1 C1-C2 // 57750 /// NM_001199061 // Wdr12 5.76E-06 2.52426NM_031156 // Ide // insulin degrading enzyme // 19 C2|19 32.24 cM // 15925 /// ENSMUST0 Ide 5.67E-07 2.52451NM_001038700 // Fnbp1 // formin binding protein 1 // 2 B|2 // 14269 /// NM_001177648 // Fnbp1 2.53E-05 2.52463NM_024264 // Cyp27a1 // cytochrome P450, family 27, subfamily a, polypeptide 1 // 1 C3| Cyp27a1 2.17E-05 2.52561AK132205 // Gm10554 // predicted gene 10554 // 18 A1|18 // 100038541 Gm10554 0.00277382 2.52606--- 0.00358885 2.52767NM_080289 // Grhpr // glyoxylate reductase/hydroxypyruvate reductase // 4|4 B2 // 76238 Grhpr 0.00141216 2.52854NM_153391 // Wdr19 // WD repeat domain 19 // 5 C3.1|5 // 213081 /// ENSMUST00000041892 Wdr19 0.000621094 2.52955--- 0.000182326 2.53016NM_018797 // Plxnc1 // plexin C1 // 10|10 C3 // 54712 /// XM_006513895 // Plxnc1 // ple Plxnc1 1.24E-06 2.53259

NM_010111 // Efnb2 // ephrin B2 // 8 A1.1|8 3.42 cM // 13642 /// ENSMUST00000001319 // Efnb2 0.000977263 2.53291NM_001253808 // Racgap1 // Rac GTPase-activating protein 1 // 15 F1|15 // 26934 /// NM_ Racgap1 8.39E-06 2.53525NM_001082532 // Pigyl // phosphatidylinositol glycan anchor biosynthesis, class Y-like Pigyl 0.00143023 2.5359NM_001134717 // 2810006K23Rik // RIKEN cDNA 2810006K23 gene // 5 F|5 // 72650 /// NM_02 2810006K23Rik 0.00435388 2.53622NM_001113470 // Ctdsp2 // CTD (carboxy-terminal domain, RNA polymerase II, polypeptide Ctdsp2 6.81E-06 2.53664NM_177586 // Eif5a2 // eukaryotic translation initiation factor 5A2 // 3 A3|3 // 208691 Eif5a2 2.20E-06 2.53727NM_177878 // Mblac1 // metallo-beta-lactamase domain containing 1 // 5 G2|5 // 330216 / Mblac1 0.00650173 2.53746ENSMUST00000028807 // Ivd // isovaleryl coenzyme A dehydrogenase // 2 E4-E5|2 // 56357 Ivd 2.72E-06 2.53899NM_008043 // Frat1 // frequently rearranged in advanced T cell lymphomas // 19 C3|19 35 Frat1 0.00159872 2.54058NM_028994 // Pck2 // phosphoenolpyruvate carboxykinase 2 (mitochondrial) // 14 C1|14 28 Pck2 0.00104994 2.54201NM_001081344 // Stxbp5 // syntaxin binding protein 5 (tomosyn) // 10|10 A2 // 78808 /// Stxbp5 1.40E-06 2.54504XM_006513283 // Lss // lanosterol synthase // 10 C1|10 39.1 cM // 16987 /// NM_146006 / Lss 7.77E-05 2.5457BC099943 // Mettl4 // methyltransferase like 4 // 17 E5|17 // 76781 /// NM_176917 // Me Mettl4 3.97E-07 2.54633NM_010295 // Gclc // glutamate-cysteine ligase, catalytic subunit // 9 D-E|9 43.36 cM / Gclc 3.40E-08 2.54667--- 0.000483835 2.54787NM_001198570 // Abi2 // abl-interactor 2 // 1 C2|1 // 329165 /// NM_001198571 // Abi2 / Abi2 0.000160514 2.55333NM_026174 // Entpd4 // ectonucleoside triphosphate diphosphohydrolase 4 // 14 D2|14 // Entpd4 3.36E-08 2.55511--- 0.00656091 2.55562ENSMUST00000181570 // Gpr137b-ps // G protein-coupled receptor 137B, pseudogene // 13 A Gpr137b-ps 0.00307687 2.55676NM_026633 // Fam195a // family with sequence similarity 195, member A // 17|17 B1 // 68 Fam195a 3.52E-05 2.55911NM_146001 // Hip1 // huntingtin interacting protein 1 // 5 F-G2|5 75.18 cM // 215114 // Hip1 1.02E-05 2.55977NM_184088 // Dennd4c // DENN/MADD domain containing 4C // 4 C4|4 // 329877 /// ENSMUST0 Dennd4c 3.20E-06 2.56546NM_001291211 // Pcmtd2 // protein-L-isoaspartate (D-aspartate) O-methyltransferase doma Pcmtd2 8.42E-06 2.56756NM_013692 // Klf10 // Kruppel-like factor 10 // 15 B3.1|15 // 21847 /// XM_006520046 // Klf10 5.89E-06 2.56863ENSMUST00000049948 // Asrgl1 // asparaginase like 1 // 19 A|19 // 66514 /// NM_025610 / Asrgl1 0.000376675 2.57046NM_001270495 // Tmem254b // transmembrane protein 254b // 14 A3|14 // 100039257 /// NM_ Tmem254b 0.000636171 2.57105NM_027495 // Tmem144 // transmembrane protein 144 // 3|3 F1 // 70652 /// XM_006502057 / Tmem144 0.000249669 2.57201ENSMUST00000172910 // Gm9581 // predicted gene 9581 // --- // --- Gm9581 0.00171962 2.57205NM_026028 // Ccdc77 // coiled-coil domain containing 77 // 6 F1|6 // 67200 /// XM_00650 Ccdc77 0.00158288 2.57539NM_001081264 // Alg6 // asparagine-linked glycosylation 6 (alpha-1,3,-glucosyltransfera Alg6 1.06E-05 2.57557ENSMUST00000102484 // Ddi2 // DNA-damage inducible protein 2 // 4 E1|4 // 68817 /// NM_ Ddi2 5.56E-08 2.57811NM_153591 // Nars2 // asparaginyl-tRNA synthetase 2 (mitochondrial)(putative) // 7 E1|7 Nars2 3.57E-06 2.57902NM_183116 // Slc18b1 // solute carrier family 18, subfamily B, member 1 // 10 A3-A4|10 Slc18b1 0.00199792 2.57917NM_178213 // Hist2h2ab // histone cluster 2, H2ab // 3 F1-F2|3 // 621893 /// ENSMUST000 Hist2h2ab 0.00468279 2.57951NM_001080949 // Ttc5 // tetratricopeptide repeat domain 5 // 14 C1|14 // 219022 /// NM_ Ttc5 9.76E-05 2.58052NM_133198 // Pygl // liver glycogen phosphorylase // 12 C2|12 29.01 cM // 110095 /// EN Pygl 2.47E-05 2.58065NM_026740 // Slc46a1 // solute carrier family 46, member 1 // 11 B5|11 46.74 cM // 5246 Slc46a1 0.00032836 2.58084NM_019537 // Psmg1 // proteasome (prosome, macropain) assembly chaperone 1 // 16 C4|16 Psmg1 0.00103021 2.58326NM_009567 // Zfp93 // zinc finger protein 93 // 7 A3|7 10.27 cM // 22755 Zfp93 0.00286977 2.58334NR_027993 // Gm3414 // predicted gene 3414 // 5 B3|5 // 100041576 /// XM_006503821 // L Gm3414 0.00110503 2.58655NM_001177878 // Phka2 // phosphorylase kinase alpha 2 // X F3-F4|X 73.95 cM // 110094 / Phka2 2.63E-07 2.58842--- 0.000463053 2.59137--- 0.00130251 2.59279NM_172578 // Mis18bp1 // MIS18 binding protein 1 // 12 C1|12 // 217653 /// ENSMUST00000 Mis18bp1 8.84E-07 2.59283NM_001037937 // Deptor // DEP domain containing MTOR-interacting protein // 15 D1|15 21 Deptor 0.000459827 2.59294NM_172600 // Tmem260 // transmembrane protein 260 // 14 C1|14 // 218989 /// XM_00651883 Tmem260 3.33E-05 2.59761NM_134126 // Ift140 // intraflagellar transport 140 // 17 A3.3|17 // 106633 /// XM_0065 Ift140 4.33E-05 2.60054NM_178724 // Harbi1 // harbinger transposase derived 1 // 2 E1|2 // 241547 /// ENSMUST0 Harbi1 0.00026665 2.60199NM_008832 // Phka1 // phosphorylase kinase alpha 1 // X D|X 45.47 cM // 18679 /// NM_17 Phka1 0.000675168 2.6032NM_010146 // Epm2a // epilepsy, progressive myoclonic epilepsy, type 2 gene alpha // 10 Epm2a 0.000209107 2.60438NM_028064 // Slc39a4 // solute carrier family 39 (zinc transporter), member 4 // 15 D3| Slc39a4 9.75E-05 2.60571NM_001168386 // Ccdc125 // coiled-coil domain containing 125 // 13 D1|13 // 76041 /// N Ccdc125 6.83E-06 2.60586NM_145599 // Tmem184c // transmembrane protein 184C // 8 C1|8 // 234463 /// XM_00653085 Tmem184c 6.48E-07 2.60714NM_001033337 // Ttc38 // tetratricopeptide repeat domain 38 // 15 E2|15 // 239570 /// X Ttc38 1.84E-05 2.60878NM_001284402 // P2rx7 // purinergic receptor P2X, ligand-gated ion channel, 7 // 5 F|5 P2rx7 4.97E-07 2.61205NM_017476 // Akap8l // A kinase (PRKA) anchor protein 8-like // 17|17 B2 // 54194 /// X Akap8l 0.00103285 2.61208NM_178772 // Nceh1 // neutral cholesterol ester hydrolase 1 // 3 A3|3 // 320024 /// ENS Nceh1 2.10E-07 2.61276NM_007620 // Cbr1 // carbonyl reductase 1 // 16 C4|16 54.53 cM // 12408 /// XM_00654334 Cbr1 0.000100905 2.61444NM_001001333 // Hexdc // hexosaminidase (glycosyl hydrolase family 20, catalytic domain Hexdc 0.000227731 2.61523NM_133740 // Prmt3 // protein arginine N-methyltransferase 3 // 7 B5|7 // 71974 /// ENS Prmt3 6.03E-07 2.61634ENSMUST00000123693 // Ptgr2 // prostaglandin reductase 2 // 12|12 D3 // 77219 /// ENSMU Ptgr2 6.57E-06 2.61745NM_001081411 // Sclt1 // sodium channel and clathrin linker 1 // 3|3 C // 67161 /// ENS Sclt1 0.000278995 2.61937NM_146033 // Ankmy2 // ankyrin repeat and MYND domain containing 2 // 12 A3|12 // 21747 Ankmy2 2.03E-06 2.62021NM_146251 // Pnpla7 // patatin-like phospholipase domain containing 7 // 2 A3|2 // 2412 Pnpla7 5.01E-06 2.6207NM_001081323 // Mphosph9 // M-phase phosphoprotein 9 // 5 F|5 // 269702 /// NM_00127786 Mphosph9 2.09E-05 2.62149NM_001033219 // Slc45a4 // solute carrier family 45, member 4 // 15 D3|15 // 106068 /// Slc45a4 0.000189591 2.62398NM_001159365 // Cep97 // centrosomal protein 97 // 16 C1.1|16 // 74201 /// NM_001159366 Cep97 0.000293145 2.62479NM_001033258 // D10Bwg1379e // DNA segment, Chr 10, Brigham & Womens Genetics 1379 expr D10Bwg1379e 1.42E-05 2.63542NM_025823 // Pcyox1 // prenylcysteine oxidase 1 // 6 D1|6 // 66881 /// ENSMUST000000320 Pcyox1 5.44E-08 2.64256--- 0.00157426 2.64464NM_001081112 // Ankrd26 // ankyrin repeat domain 26 // 6 F1|6 // 232339 /// ENSMUST0000 Ankrd26 0.000620317 2.64518NM_001285463 // Carf // calcium response factor // 1 C2|1 // 241066 /// NM_001285473 // Carf 0.00020665 2.64554NR_045187 // 4833417C18Rik // RIKEN cDNA 4833417C18 gene // 11|11 // 73906 /// ENSMUST0 4833417C18Rik 0.000572211 2.6476AK047378 // Chst10 // carbohydrate sulfotransferase 10 // 1 B|1 // 98388 /// NM_145142 Chst10 0.000236003 2.64871NM_009908 // Cmas // cytidine monophospho-N-acetylneuraminic acid synthetase // 6 G3|6 Cmas 4.01E-07 2.65031NM_001145967 // Atg4c // autophagy related 4C, cysteine peptidase // 4 C6|4 // 242557 / Atg4c 8.23E-06 2.65214NM_146184 // B3gnt8 // UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 8 // B3gnt8 0.000728594 2.65464NM_146171 // Ncapd2 // non-SMC condensin I complex, subunit D2 // 6|6 F2 // 68298 /// E Ncapd2 0.000460065 2.65481NM_008611 // Mmp8 // matrix metallopeptidase 8 // 9 A1|9 // 17394 /// ENSMUST0000001876 Mmp8 8.32E-05 2.65492NM_175507 // Slc35g1 // solute carrier family 35, member G1 // 19 C3|19 // 240660 /// E Slc35g1 4.22E-05 2.66085NM_008397 // Itga6 // integrin alpha 6 // 2 C2-C3|2 42.79 cM // 16403 /// NM_001277970 Itga6 6.81E-06 2.66139NM_145382 // Fam193b // family with sequence similarity 193, member B // 13 B1|13 // 21 Fam193b 0.00344414 2.66763NM_001281980 // Lrmp // lymphoid-restricted membrane protein // 6 G3|6 77.34 cM // 1697 Lrmp 1.57E-05 2.66884NM_009370 // Tgfbr1 // transforming growth factor, beta receptor I // 4 B1|4 26.02 cM / Tgfbr1 1.43E-06 2.66997--- 0.00579942 2.67091NM_001276452 // Slc17a5 // solute carrier family 17 (anion/sugar transporter), member 5 Slc17a5 2.27E-06 2.67579NM_007533 // Bckdha // branched chain ketoacid dehydrogenase E1, alpha polypeptide // 7 Bckdha 4.25E-05 2.67718NM_138586 // Exosc5 // exosome component 5 // 7 A3|7 13.96 cM // 27998 /// NR_104358 // Exosc5 0.000516586 2.67782NM_029420 // Slx1b // SLX1 structure-specific endonuclease subunit homolog B (S. cerevi Slx1b 0.000402117 2.67802NM_183034 // Plekhm1 // pleckstrin homology domain containing, family M (with RUN domai Plekhm1 8.10E-06 2.67871--- 0.000569009 2.68117NM_172562 // Tada2a // transcriptional adaptor 2A // 11 C|11 // 217031 /// XM_006532989 Tada2a 5.22E-06 2.68375NM_001081040 // Coq10a // coenzyme Q10 homolog A (yeast) // 10 D3|10 // 210582 /// XM_0 Coq10a 4.72E-05 2.68466

NM_001253692 // Elmod3 // ELMO/CED-12 domain containing 3 // 6 C1|6 // 232089 /// NM_14 Elmod3 0.00209912 2.68583NM_146069 // Nrros // negative regulator of reactive oxygen species // 16 B2|16 // 2241 Nrros 4.77E-07 2.69018NM_001025250 // Vegfa // vascular endothelial growth factor A // 17 C|17 22.79 cM // 22 Vegfa 6.80E-09 2.69066--- 0.00022364 2.69373NR_036450 // Gm14403 // predicted gene 14403 // 2 H4|2 // 433520 Gm14403 0.000620805 2.69477NM_001290782 // Accs // 1-aminocyclopropane-1-carboxylate synthase (non-functional) // Accs 5.27E-05 2.69505NM_001033441 // Alg10b // asparagine-linked glycosylation 10B (alpha-1,2-glucosyltransf Alg10b 1.68E-06 2.69672NM_001252220 // Nbr1 // neighbor of Brca1 gene 1 // 11 D|11 65.36 cM // 17966 /// NM_00 Nbr1 2.75E-07 2.69945NM_007496 // Zfhx3 // zinc finger homeobox 3 // 8|8 E1 // 11906 /// XM_006530586 // Zfh Zfhx3 2.65E-05 2.69953XR_401386 // 4930555A03Rik // RIKEN cDNA 4930555A03 gene // 3|3 // 100504653 /// AK0088 4930555A03Rik 0.00203385 2.70075NM_133976 // Imp3 // IMP3, U3 small nucleolar ribonucleoprotein, homolog (yeast) // 9 B Imp3 4.06E-05 2.7063NM_001177568 // Gm14420 // predicted gene 14420 // 2 H4|2 // 628308 Gm14420 1.60E-05 2.7064--- 0.00449835 2.70678NM_001199304 // Atxn1 // ataxin 1 // 13 A5|13 21.98 cM // 20238 /// NM_001199305 // Atx Atxn1 0.000151581 2.70836NM_011305 // Rxra // retinoid X receptor alpha // 2 A3|2 19.38 cM // 20181 /// ENSMUST0 Rxra 3.99E-06 2.70996NM_001017983 // Foxred2 // FAD-dependent oxidoreductase domain containing 2 // 15 E1|15 Foxred2 0.000137655 2.71018--- 0.00377473 2.71051--- 0.00425176 2.71079NM_028959 // Cep72 // centrosomal protein 72 // 13 C1|13 // 74470 /// ENSMUST0000003645 Cep72 0.000147891 2.71452NM_001039472 // Kif21b // kinesin family member 21B // 1 E4|1 59.61 cM // 16565 /// ENS Kif21b 5.78E-05 2.71461--- 3.04E-05 2.71528ENSMUST00000140646 // Gm15513 // predicted gene 15513 // --- // --- Gm15513 0.00195072 2.71662NM_001081278 // Tbc1d4 // TBC1 domain family, member 4 // 14 E2.3|14 // 210789 /// XM_0 Tbc1d4 2.58E-05 2.71812NM_025790 // Acot13 // acyl-CoA thioesterase 13 // 13|13 A3.2 // 66834 /// ENSMUST00000 Acot13 3.87E-06 2.72298NM_011828 // Hs2st1 // heparan sulfate 2-O-sulfotransferase 1 // 3 H2|3 // 23908 /// XM Hs2st1 4.53E-05 2.72371NM_010560 // Il6st // interleukin 6 signal transducer // 13 D2.2|13 63.73 cM // 16195 / Il6st 5.93E-08 2.72464NM_172146 // Ppat // phosphoribosyl pyrophosphate amidotransferase // 5 C3.3|5 // 23132 Ppat 0.00024324 2.72522NM_139138 // Emr4 // EGF-like module containing, mucin-like, hormone receptor-like sequ Emr4 0.00070726 2.72687NM_145223 // Alms1 // Alstrom syndrome 1 // 6 C3|6 // 236266 /// ENSMUST00000072018 // Alms1 0.00098987 2.72746NM_001164426 // Kcnk13 // potassium channel, subfamily K, member 13 // 12 E|12 // 21782 Kcnk13 0.000722092 2.72906NM_001130416 // Hdac6 // histone deacetylase 6 // X A1.1|X 3.58 cM // 15185 /// NM_0104 Hdac6 3.11E-05 2.72992NM_001115018 // Suv420h2 // suppressor of variegation 4-20 homolog 2 (Drosophila) // 7 Suv420h2 9.28E-05 2.73123NM_010247 // Xrcc6 // X-ray repair complementing defective repair in Chinese hamster ce Xrcc6 3.25E-05 2.73189NM_028131 // Cenpn // centromere protein N // 8 E1|8 // 72155 /// ENSMUST00000034205 // Cenpn 0.000153619 2.73318NM_172631 // Ldlrad4 // low density lipoprotein receptor class A domain containing 4 // Ldlrad4 1.63E-05 2.73513NM_153587 // Rps6ka5 // ribosomal protein S6 kinase, polypeptide 5 // 12 E|12 // 73086 Rps6ka5 8.52E-05 2.73631--- 0.000657977 2.73909NM_177366 // Gpr157 // G protein-coupled receptor 157 // 4 E2|4 // 269604 /// ENSMUST00 Gpr157 5.49E-05 2.73919NM_023203 // Dctpp1 // dCTP pyrophosphatase 1 // 7 F3|7 // 66422 /// ENSMUST00000035276 Dctpp1 0.0003108 2.74319NM_027100 // Rwdd2a // RWD domain containing 2A // 9 E3.1|9 // 69519 /// ENSMUST0000003 Rwdd2a 0.00402283 2.74995NM_001271357 // Flcn // folliculin // 11 B1.3|11 // 216805 /// NR_073164 // Flcn // fol Flcn 8.14E-08 2.75593NM_177151 // Vps13b // vacuolar protein sorting 13B (yeast) // 15 B3.1|15 // 666173 /// Vps13b 5.11E-08 2.75676NM_001159572 // 4632428N05Rik // RIKEN cDNA 4632428N05 gene // 10 B4|10 // 74048 /// NM 4632428N05Rik 3.16E-07 2.75901NM_001195537 // Smpd5 // sphingomyelin phosphodiesterase 5 // 15 D3|15 // 100503915 /// Smpd5 0.000344613 2.76489NM_025864 // Tmem206 // transmembrane protein 206 // 1 H6|1 // 66950 /// ENSMUST0000002 Tmem206 6.16E-06 2.76633NM_145359 // Ubald1 // UBA-like domain containing 1 // 16 A1|16 // 207740 /// ENSMUST00 Ubald1 7.92E-05 2.7665NM_001033606 // Acsl3 // acyl-CoA synthetase long-chain family member 3 // 1 C4|1 40.84 Acsl3 0.000146507 2.76697NM_175265 // Bora // bora, aurora kinase A activator // 14 E2.2|14 // 77744 /// XM_0065 Bora 0.00263326 2.77277NM_001285917 // Dapk1 // death associated protein kinase 1 // 13 B2|13 32.53 cM // 6963 Dapk1 1.91E-07 2.77487NM_001008501 // Zfp760 // zinc finger protein 760 // 17 A3.2-A3.3|17 // 240034 /// ENSM Zfp760 0.00035331 2.77606NM_001163734 // Rrp1b // ribosomal RNA processing 1 homolog B (S. cerevisiae) // 17 B1| Rrp1b 1.01E-05 2.77677NM_175383 // B3gnt1 // UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 1 // B3gnt1 7.39E-06 2.77801XR_393428 // Gm11423 // predicted gene 11423 // 11|11 50.23 cM // 100503272 /// ENSMUST Gm11423 8.14E-07 2.78144NM_009012 // Rad50 // RAD50 homolog (S. cerevisiae) // 11 A5-B1|11 31.98 cM // 19360 // Rad50 1.93E-06 2.78989NM_001290792 // Wdr45 // WD repeat domain 45 // X A1.1|X 3.48 cM // 54636 /// NM_001290 Wdr45 1.16E-07 2.79302NM_029762 // Hyls1 // hydrolethalus syndrome 1 // 9 A4|9 // 76832 /// ENSMUST0000011511 Hyls1 0.000414415 2.79327NM_001166406 // Kif20a // kinesin family member 20A // 18 B1|18 18.69 cM // 19348 /// N Kif20a 8.35E-06 2.79463NM_001014981 // Wdr7 // WD repeat domain 7 // 18|18 D1-E3 // 104082 /// ENSMUST00000072 Wdr7 9.79E-06 2.7956NM_009266 // Sephs2 // selenophosphate synthetase 2 // 7 F3|7 69.43 cM // 20768 /// AK0 Sephs2 6.19E-06 2.79939AK032971 // Gm11974 // predicted gene 11974 // 11 A1|11 // 100041286 Gm11974 0.0057794 2.80212ENSMUST00000082675 // Gm25635 // predicted gene, 25635 // --- // --- Gm25635 0.000228135 2.80446--- 0.00411694 2.80481NM_145564 // Fbxo21 // F-box protein 21 // 5 F|5 // 231670 /// ENSMUST00000035579 // Fb Fbxo21 1.47E-05 2.80492--- 2.35E-05 2.80698NM_001081415 // Samd1 // sterile alpha motif domain containing 1 // 8 C3|8 // 666704 // Samd1 1.55E-05 2.81058NM_011638 // Tfrc // transferrin receptor // 16 B3|16 23.06 cM // 22042 /// ENSMUST0000 Tfrc 4.61E-08 2.81278NM_029600 // Abcc3 // ATP-binding cassette, sub-family C (CFTR/MRP), member 3 // 11 D|1 Abcc3 2.73E-08 2.81726ENSMUST00000001331 // Myg1 // melanocyte proliferating gene 1 // 15 F3|15 // 60315 /// Myg1 1.20E-05 2.81867NM_001122818 // Pnpla6 // patatin-like phospholipase domain containing 6 // 8 A1.1|8 1. Pnpla6 1.61E-05 2.81947NM_001042655 // Tbc1d17 // TBC1 domain family, member 17 // 7 B4|7 // 233204 /// ENSMUS Tbc1d17 3.21E-05 2.82064ENSMUST00000085206 // Slc25a36 // solute carrier family 25, member 36 // 9 E3.3|9 // 19 Slc25a36 1.11E-06 2.82263NM_001256522 // C330006A16Rik // RIKEN cDNA C330006A16 gene // 2 A3|2 // 109299 C330006A16Rik 0.00242339 2.82506NM_133976 // Imp3 // IMP3, U3 small nucleolar ribonucleoprotein, homolog (yeast) // 9 B Imp3 0.000218844 2.82547XM_006518799 // Tsc22d1 // TSC22 domain family, member 1 // 14 D3|14 40.44 cM // 21807 Tsc22d1 4.40E-05 2.82556NM_001039534 // Pstk // phosphoseryl-tRNA kinase // 7 F3|7 // 214580 /// ENSMUST0000007 Pstk 1.06E-05 2.82783NM_173733 // Suox // sulfite oxidase // 10 D3|10 // 211389 /// ENSMUST00000054764 // Su Suox 0.000528703 2.83086NM_007420 // Adrb2 // adrenergic receptor, beta 2 // 18 E1|18 35.1 cM // 11555 /// ENSM Adrb2 0.000699832 2.83144NM_173865 // Slc41a1 // solute carrier family 41, member 1 // 1 E4|1 // 98396 /// ENSMU Slc41a1 2.56E-06 2.83278NM_025370 // Aaed1 // AhpC/TSA antioxidant enzyme domain containing 1 // 13 B3|13 // 66 Aaed1 4.75E-07 2.83451NM_001040130 // Tmem141 // transmembrane protein 141 // 2 A3|2 17.57 cM // 51875 /// NM Tmem141 1.90E-05 2.84082NM_028390 // Anln // anillin, actin binding protein // 9|9 A4 // 68743 /// XM_006510581 Anln 0.000458143 2.841NM_175542 // Rttn // rotatin // 18 E4|18 // 246102 /// ENSMUST00000023828 // Rttn // ro Rttn 1.37E-05 2.84105NM_026641 // Ift80 // intraflagellar transport 80 // 3|3 E2 // 68259 /// XM_006501966 / Ift80 0.000161471 2.84195NM_194348 // Atg2a // autophagy related 2A // 19 A|19 // 329015 /// ENSMUST00000045351 Atg2a 1.42E-05 2.84237NM_027279 // Mettl18 // methyltransferase like 18 // 1 H2.2|1 // 69962 /// ENSMUST00000 Mettl18 0.000133066 2.8458NM_022017 // Trpv4 // transient receptor potential cation channel, subfamily V, member Trpv4 0.000279161 2.85691NM_175403 // Mlec // malectin // 5 F|5 55.99 cM // 109154 /// ENSMUST00000053271 // Mle Mlec 1.81E-08 2.85731NM_001168615 // Tifab // TRAF-interacting protein with forkhead-associated domain, fami Tifab 1.04E-06 2.85788NM_001168288 // Arhgap39 // Rho GTPase activating protein 39 // 15 D3|15 36.28 cM // 22 Arhgap39 0.000120001 2.85837NM_053169 // Trim16 // tripartite motif-containing 16 // 11 B2|11 // 94092 /// ENSMUST0 Trim16 1.59E-05 2.8621NM_001252654 // Kcnab2 // potassium voltage-gated channel, shaker-related subfamily, be Kcnab2 0.000212713 2.86355NM_152801 // Arhgef6 // Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6 // X A5|X Arhgef6 1.39E-05 2.86725NM_001037937 // Deptor // DEP domain containing MTOR-interacting protein // 15 D1|15 21 Deptor 6.17E-05 2.86776

NM_001110193 // Inpp5d // inositol polyphosphate-5-phosphatase D // 1 C5|1 44.44 cM // Inpp5d 2.48E-06 2.86954NR_037996 // Hmga2-ps1 // high mobility group AT-hook 2, pseudogene 1 // 1|1 // 15365 Hmga2-ps1 3.88E-05 2.87222NM_001177806 // Eif2ak4 // eukaryotic translation initiation factor 2 alpha kinase 4 // Eif2ak4 1.44E-05 2.87759NM_030719 // Gatsl2 // GATS protein-like 2 // 5|5 G1 // 80909 /// ENSMUST00000016088 // Gatsl2 1.74E-05 2.87916NM_001080557 // Vamp1 // vesicle-associated membrane protein 1 // 6 F3|6 59.32 cM // 22 Vamp1 0.000483196 2.88027--- 1.19E-05 2.88265NM_177305 // Arl4c // ADP-ribosylation factor-like 4C // 1 D|1 // 320982 /// ENSMUST000 Arl4c 1.70E-06 2.88496NM_207301 // Wrb // tryptophan rich basic protein // 16 C4|16 // 71446 /// XM_006523091 Wrb 3.66E-05 2.88888NM_012048 // Polk // polymerase (DNA directed), kappa // 13 D1|13 // 27015 /// XM_00651 Polk 1.22E-05 2.89087ENSMUST00000001455 // Mef2d // myocyte enhancer factor 2D // 3 F1|3 38.78 cM // 17261 / Mef2d 5.30E-05 2.89241NM_181325 // Slc25a15 // solute carrier family 25 (mitochondrial carrier ornithine tran Slc25a15 1.40E-05 2.89703NM_130450 // Elovl6 // ELOVL family member 6, elongation of long chain fatty acids (yea Elovl6 4.22E-05 2.90345NM_178415 // Bbs9 // Bardet-Biedl syndrome 9 (human) // 9 A3|9 // 319845 /// NM_181316 Bbs9 1.36E-05 2.9039NM_027188 // Smyd3 // SET and MYND domain containing 3 // 1 H3|1 83.48 cM // 69726 /// Smyd3 4.24E-06 2.90448NM_001170537 // Mef2c // myocyte enhancer factor 2C // 13 C3|13 43.68 cM // 17260 /// N Mef2c 1.06E-07 2.90588NM_175518 // Tmem245 // transmembrane protein 245 // 4 B3|4 // 242474 /// ENSMUST000000 Tmem245 6.32E-06 2.9085NM_001037136 // Agap1 // ArfGAP with GTPase domain, ankyrin repeat and PH domain 1 // 1 Agap1 6.71E-06 2.91039NM_001039551 // Cnnm3 // cyclin M3 // 1 B|1 15.3 cM // 94218 /// NM_053186 // Cnnm3 // Cnnm3 4.52E-06 2.91081NM_008212 // Hadh // hydroxyacyl-Coenzyme A dehydrogenase // 3 G3|3 // 15107 /// ENSMUS Hadh 4.53E-06 2.9119NM_029128 // Qtrtd1 // queuine tRNA-ribosyltransferase domain containing 1 // 16 B4|16 Qtrtd1 0.000109424 2.91803NM_013753 // Pald1 // phosphatase domain containing, paladin 1 // 10 B4|10 // 27355 /// Pald1 0.000307498 2.92377NM_001205181 // Abhd4 // abhydrolase domain containing 4 // 14 C2|14 // 105501 /// NM_1 Abhd4 1.96E-06 2.92427NM_199467 // Mms22l // MMS22-like, DNA repair protein // 4 A3|4 // 212377 /// ENSMUST00 Mms22l 6.65E-05 2.92756NM_010615 // Kif11 // kinesin family member 11 // 19 C2|19 // 16551 /// ENSMUST00000012 Kif11 1.17E-07 2.92922ENSMUST00000181502 // Gm17586 // predicted gene, 17586 // --- // --- /// AK142663 // Gm Gm17586 0.000511537 2.93016ENSMUST00000032803 // Zfp30 // zinc finger protein 30 // 7 B1|7 17.26 cM // 22693 /// E Zfp30 0.00263603 2.93356NM_001291910 // Adcy9 // adenylate cyclase 9 // 16 B1|16 2.42 cM // 11515 /// NM_009624 Adcy9 0.000202221 2.9363NM_001159626 // Hagh // hydroxyacyl glutathione hydrolase // 17 A3.3|17 12.53 cM // 146 Hagh 3.51E-06 2.93872NM_001290514 // Mospd1 // motile sperm domain containing 1 // X|X A4 // 70380 /// NM_02 Mospd1 4.65E-08 2.94017NM_008389 // Ipp // IAP promoted placental gene // 4 D1|4 53.2 cM // 16351 /// XM_00650 Ipp 0.000475389 2.94082ENSMUST00000092720 // 5430403G16Rik // RIKEN cDNA 5430403G16 gene // --- // --- 5430403G16Rik 0.000774639 2.94321NM_001136236 // Fcrl1 // Fc receptor-like 1 // 3 F1|3 // 229499 /// NM_153090 // Fcrl1 Fcrl1 8.43E-05 2.94322NM_199029 // Zfp395 // zinc finger protein 395 // 14 D1|14 // 380912 /// ENSMUST0000006 Zfp395 0.000411841 2.94763NM_001271599 // Sort1 // sortilin 1 // 3 F3|3 // 20661 /// NM_019972 // Sort1 // sortil Sort1 1.52E-08 2.94881NM_028773 // Sash3 // SAM and SH3 domain containing 3 // X A4|X // 74131 /// ENSMUST000 Sash3 6.34E-06 2.94917NM_172619 // Adamts10 // a disintegrin-like and metallopeptidase (reprolysin type) with Adamts10 0.000179221 2.95117--- 0.004088 2.95178NM_009644 // Ahrr // aryl-hydrocarbon receptor repressor // 13 C2|13 // 11624 /// XM_00 Ahrr 5.16E-05 2.95687NM_001077353 // Gsta3 // glutathione S-transferase, alpha 3 // 1 A4|1 6.5 cM // 14859 / Gsta3 0.000694357 2.96018NM_019986 // Habp4 // hyaluronic acid binding protein 4 // 13 B3|13 33.26 cM // 56541 / Habp4 6.61E-06 2.9605NM_029999 // Lbh // limb-bud and heart // 17 E2|17 // 77889 /// ENSMUST00000024857 // L Lbh 7.44E-07 2.96453NM_001033164 // 2510002D24Rik // RIKEN cDNA 2510002D24 gene // 16 A3|16 // 72307 /// EN 2510002D24Rik 0.000944933 2.96579NM_001102471 // Cnnm2 // cyclin M2 // 19 C3|19 38.97 cM // 94219 /// NM_033569 // Cnnm2 Cnnm2 0.000205696 2.96666XM_006513183 // Cradd // CASP2 and RIPK1 domain containing adaptor with death domain // Cradd 4.82E-06 2.97087NM_008979 // Ptpn22 // protein tyrosine phosphatase, non-receptor type 22 (lymphoid) // Ptpn22 2.82E-07 2.9715--- 0.000393905 2.97445--- 4.72E-05 2.98173NM_001033385 // Tbc1d32 // TBC1 domain family, member 32 // 10 B3|10 // 544696 /// ENSM Tbc1d32 2.10E-05 2.9824NM_001008542 // Mxi1 // Max interacting protein 1 // 19 D|19 47.53 cM // 17859 /// NM_0 Mxi1 7.63E-09 2.98338NM_001166493 // Rasgrp3 // RAS, guanyl releasing protein 3 // 17 E2|17 // 240168 /// NM Rasgrp3 1.07E-06 2.99087NM_027288 // Manba // mannosidase, beta A, lysosomal // 3 H2|3 62.65 cM // 110173 /// E Manba 2.43E-07 2.99117NR_045696 // 9330133O14Rik // RIKEN cDNA 9330133O14 gene // 8 E1 // 100689703 9330133O14Rik 4.81E-05 2.99465NM_144804 // Depdc7 // DEP domain containing 7 // 2 E2|2 // 211896 /// ENSMUST000000285 Depdc7 8.88E-06 3.00235NM_001178012 // Sfxn3 // sideroflexin 3 // 19|19 D1 // 94280 /// NM_001178013 // Sfxn3 Sfxn3 4.45E-06 3.00597ENSMUST00000148876 // Mettl8 // methyltransferase like 8 // 2 C2|2 // 228019 /// NM_001 Mettl8 4.81E-05 3.00854NM_001044744 // Gcdh // glutaryl-Coenzyme A dehydrogenase // 8 C3|8 41.28 cM // 270076 Gcdh 3.37E-09 3.01073ENSMUST00000000896 // Pxmp4 // peroxisomal membrane protein 4 // 2|2 H2 // 59038 /// NM Pxmp4 1.69E-06 3.0183NM_001276455 // Slc19a2 // solute carrier family 19 (thiamine transporter), member 2 // Slc19a2 3.01E-07 3.01955NM_001047604 // Ttc21b // tetratricopeptide repeat domain 21B // 2 C1.3|2 // 73668 /// Ttc21b 0.000238114 3.0214NM_009029 // Rb1 // retinoblastoma 1 // 14 D3|14 38.73 cM // 19645 /// XR_383150 // Rb1 Rb1 1.81E-07 3.0228NM_177683 // Vgll4 // vestigial like 4 (Drosophila) // 6 E3|6 // 232334 /// XM_00650601 Vgll4 2.63E-05 3.02417NM_001293637 // Nek1 // NIMA (never in mitosis gene a)-related expressed kinase 1 // 8 Nek1 0.000171816 3.03282NM_026916 // Nupr1l // nuclear protein transcriptional regulator 1 like // 5|5 // 69034 Nupr1l 6.53E-06 3.03377NM_009577 // Zik1 // zinc finger protein interacting with K protein 1 // 7 A1|7 // 2277 Zik1 0.00186189 3.03812NM_001004062 // Crtc1 // CREB regulated transcription coactivator 1 // 8 B3.3|8 // 3820 Crtc1 1.57E-07 3.03818NM_153571 // Hscb // HscB iron-sulfur cluster co-chaperone homolog (E. coli) // 5 F|5 / Hscb 9.07E-06 3.03991--- 0.00368352 3.042NM_001159559 // Xrcc6bp1 // XRCC6 binding protein 1 // 10 D3|10 // 68876 /// ENSMUST000 Xrcc6bp1 0.000218516 3.04519--- 0.000300899 3.04668NM_008924 // Prkar2a // protein kinase, cAMP dependent regulatory, type II alpha // 9 F Prkar2a 4.33E-07 3.04781NM_001081259 // Mfsd7b // major facilitator superfamily domain containing 7B // 1 H6|1 Mfsd7b 1.51E-07 3.04977NR_029535 // Mir99a // microRNA 99a // 16|16 // 387229 /// ENSMUST00000083596 // Mir99a Mir99a 0.000776735 3.05059NM_001004362 // 2610008E11Rik // RIKEN cDNA 2610008E11 gene // 10 C1|10 // 72128 /// EN 2610008E11Rik 0.000392035 3.05648NM_010511 // Ifngr1 // interferon gamma receptor 1 // 10 A3|10 8.49 cM // 15979 /// ENS Ifngr1 7.19E-06 3.05677NM_001038703 // Gpr146 // G protein-coupled receptor 146 // 5|5 G1 // 80290 /// ENSMUST Gpr146 2.26E-05 3.05682NM_172573 // Engase // endo-beta-N-acetylglucosaminidase // 11 E2|11 // 217364 /// ENSM Engase 0.000109172 3.06647NM_001162375 // Fam73a // family with sequence similarity 73, member A // 3 H3|3 // 215 Fam73a 6.44E-05 3.06746NM_153177 // Ago4 // argonaute RISC catalytic subunit 4 // 4 D2.2|4 // 76850 /// ENSMUS Ago4 0.00160879 3.07145NM_001290633 // Reps2 // RALBP1 associated Eps domain containing protein 2 // X F4|X // Reps2 1.22E-06 3.07448NM_020332 // Ank // progressive ankylosis // 15 B1|15 10.23 cM // 11732 /// ENSMUST0000 Ank 6.30E-07 3.07986NM_010830 // Msh6 // mutS homolog 6 (E. coli) // 17 E4|17 57.87 cM // 17688 /// ENSMUST Msh6 1.52E-05 3.08029NM_025464 // Tmem218 // transmembrane protein 218 // 9 A4|9 // 66279 /// XM_006510545 / Tmem218 2.43E-05 3.08186NM_001289589 // Zfp12 // zinc finger protein 12 // 5 G2|5 // 231866 /// NM_001289590 // Zfp12 1.39E-05 3.08548NM_019426 // Atf7ip // activating transcription factor 7 interacting protein // 6 G1|6 Atf7ip 5.43E-08 3.08726NM_001081266 // Ccdc142 // coiled-coil domain containing 142 // 6 C3|6 // 243510 /// EN Ccdc142 0.000253712 3.08816ENSMUST00000157170 // Gm25965 // predicted gene, 25965 // --- // --- Gm25965 0.00142263 3.09083--- 0.00294985 3.09435NM_019811 // Acss2 // acyl-CoA synthetase short-chain family member 2 // 2|2 H2 // 6052 Acss2 7.97E-08 3.09747NM_175331 // Nt5dc3 // 5-nucleotidase domain containing 3 // 10 C1|10 // 103466 /// ENS Nt5dc3 2.10E-06 3.09788NR_015524 // Cep83os // centrosomal protein 83, opposite strand // 10 C2|10 // 67723 // Cep83os 0.00203811 3.09922NM_175511 // Fam78a // family with sequence similarity 78, member A // 2 B|2 // 241303 Fam78a 2.39E-05 3.10006NM_027629 // Pgm2l1 // phosphoglucomutase 2-like 1 // 7|7 F1 // 70974 /// XM_006508205 Pgm2l1 3.70E-07 3.10183NM_007671 // Cdkn2c // cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) // 4 C Cdkn2c 0.000401537 3.10631

NM_028469 // 3110082I17Rik // RIKEN cDNA 3110082I17 gene // 5 G2|5 // 73212 /// XM_0065 3110082I17Rik 3.52E-05 3.11227NM_030229 // Polr3h // polymerase (RNA) III (DNA directed) polypeptide H // 15|15 E2 // Polr3h 0.00074933 3.11568NR_001461 // Kcnq1ot1 // KCNQ1 overlapping transcript 1 // 7 F5|7 88.15 cM // 63830 Kcnq1ot1 0.00344788 3.12272NM_010121 // Eif2ak3 // eukaryotic translation initiation factor 2 alpha kinase 3 // 6 Eif2ak3 8.38E-06 3.12411NM_172694 // Megf9 // multiple EGF-like-domains 9 // 4 C2|4 // 230316 /// ENSMUST000001 Megf9 2.84E-06 3.12498NM_001115130 // Zbtb44 // zinc finger and BTB domain containing 44 // 9 A4|9 // 235132 Zbtb44 1.03E-06 3.13115ENSMUST00000134311 // Fos // FBJ osteosarcoma oncogene // 12 D2|12 39.7 cM // 14281 /// Fos 1.66E-08 3.13186NM_181071 // Tanc2 // tetratricopeptide repeat, ankyrin repeat and coiled-coil containi Tanc2 7.79E-07 3.13339NM_199308 // Mast3 // microtubule associated serine/threonine kinase 3 // 8 B3.3|8 // 5 Mast3 0.000550939 3.1399NM_001195088 // Tmc8 // transmembrane channel-like gene family 8 // 11 E2|11 // 217356 Tmc8 1.99E-06 3.14368NM_145460 // Oxnad1 // oxidoreductase NAD-binding domain containing 1 // 14 B|14 // 218 Oxnad1 0.000165483 3.14568NM_001170489 // Aplf // aprataxin and PNKP like factor // 6 D1|6 // 72103 /// NM_024251 Aplf 8.55E-06 3.14718NM_198105 // Fam120c // family with sequence similarity 120, member C // X|X F2 // 2073 Fam120c 6.35E-06 3.15098--- 0.00396231 3.15541NM_008079 // Galc // galactosylceramidase // 12 E|12 49.83 cM // 14420 /// ENSMUST00000 Galc 9.75E-06 3.15741NM_133218 // Zfp704 // zinc finger protein 704 // 3 A1|3 // 170753 /// ENSMUST000000411 Zfp704 1.46E-06 3.16354NM_001128606 // Epb4.1 // erythrocyte protein band 4.1 // 4 D2.3|4 64.54 cM // 269587 / Epb4.1 0.000122362 3.16496NM_026543 // 3010026O09Rik // RIKEN cDNA 3010026O09 gene // 11 B1.3|11 // 68067 /// ENS 3010026O09Rik 0.000413827 3.16855NM_139232 // Fgd4 // FYVE, RhoGEF and PH domain containing 4 // 16 A3|16 // 224014 /// Fgd4 2.42E-06 3.1775NM_026065 // Mrpl42 // mitochondrial ribosomal protein L42 // 10 C2|10 49.39 cM // 6727 Mrpl42 0.000874324 3.18786NM_008131 // Glul // glutamate-ammonia ligase (glutamine synthetase) // 1 G2|1 // 14645 Glul 6.42E-08 3.2017NM_001290784 // Ldlrad3 // low density lipoprotein receptor class A domain containing 3 Ldlrad3 3.08E-05 3.21227NM_025969 // Timm21 // tranlocase of inner mitochondrial membrane 21 // 18|18 E3 // 671 Timm21 0.000148724 3.21331NM_008841 // Pik3r2 // phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 2 Pik3r2 8.21E-06 3.21521NM_133185 // Rogdi // rogdi homolog (Drosophila) // 16 A1|16 2.49 cM // 66049 /// XM_00 Rogdi 1.93E-05 3.2154NM_001030293 // Spry3 // sprouty homolog 3 (Drosophila) // --- // 236576 /// ENSMUST000 Spry3 2.84E-06 3.21642NM_009531 // Xpc // xeroderma pigmentosum, complementation group C // 6|6 D // 22591 // Xpc 1.62E-08 3.21876NM_133931 // Pot1a // protection of telomeres 1A // 6 A3.1|6 // 101185 /// ENSMUST00000 Pot1a 3.12E-05 3.22246NM_172779 // Ddx26b // DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 26B // X A5|X // 23 Ddx26b 5.79E-05 3.22247NM_001177625 // Ect2 // ect2 oncogene // 3|3 B // 13605 /// NM_001177626 // Ect2 // ect Ect2 2.18E-05 3.22799NM_172926 // Snx14 // sorting nexin 14 // 9 E3.1|9 // 244962 /// XM_006511181 // Snx14 Snx14 3.21E-06 3.2282NM_023645 // Kdelc1 // KDEL (Lys-Asp-Glu-Leu) containing 1 // 1|1 C1 // 72050 /// XM_00 Kdelc1 8.13E-07 3.22958NM_178253 // Klhdc1 // kelch domain containing 1 // 12 C2|12 // 271005 /// XM_006515928 Klhdc1 0.000310588 3.23016NM_007642 // Cd28 // CD28 antigen // 1 C1-C3|1 30.52 cM // 12487 /// ENSMUST00000027165 Cd28 2.76E-05 3.23055NM_176996 // Smo // smoothened homolog (Drosophila) // 6 A3.3|6 12.36 cM // 319757 /// Smo 1.36E-05 3.23419--- 0.000173999 3.24272NM_133829 // Mfsd6 // major facilitator superfamily domain containing 6 // 1 C1.1|1 // Mfsd6 1.80E-06 3.26017BC049272 // Kif18b // kinesin family member 18B // 11 E1|11 // 70218 /// NM_197959 // K Kif18b 0.00154197 3.26132NM_178113 // Ncapd3 // non-SMC condensin II complex, subunit D3 // 9 A4|9 // 78658 /// Ncapd3 1.94E-07 3.26341--- 0.00171292 3.26408NM_133667 // Pdk2 // pyruvate dehydrogenase kinase, isoenzyme 2 // 11 D|11 59.01 cM // Pdk2 0.000140508 3.26552NM_008152 // Gpr65 // G-protein coupled receptor 65 // 12 E|12 // 14744 /// ENSMUST0000 Gpr65 3.09E-08 3.2658XM_006533512 // Slc22a4 // solute carrier family 22 (organic cation transporter), membe Slc22a4 1.03E-06 3.26965NR_030698 // A630066F11Rik // RIKEN cDNA A630066F11 gene // 10|10 // 320642 A630066F11Rik 0.00239758 3.27053NM_008517 // Lta4h // leukotriene A4 hydrolase // 10|10 C3 // 16993 /// ENSMUST00000016 Lta4h 1.33E-05 3.27174NM_027289 // Nt5dc2 // 5-nucleotidase domain containing 2 // 14 B|14 // 70021 /// ENSMU Nt5dc2 2.65E-07 3.27272NM_001199283 // Slc43a2 // solute carrier family 43, member 2 // 11 B5|11 // 215113 /// Slc43a2 6.78E-07 3.27417NM_011385 // Ski // ski sarcoma viral oncogene homolog (avian) // 4 E2|4 86.17 cM // 20 Ski 7.58E-06 3.27534NM_026260 // Tctn3 // tectonic family member 3 // 19 C3|19 // 67590 /// ENSMUST00000025 Tctn3 1.15E-07 3.27995NM_001293701 // Polr3gl // polymerase (RNA) III (DNA directed) polypeptide G like // 3 Polr3gl 1.43E-06 3.28026NM_001081433 // Ankrd44 // ankyrin repeat domain 44 // 1 C1.1|1 // 329154 /// ENSMUST00 Ankrd44 2.08E-07 3.2861NM_001162947 // Nek3 // NIMA (never in mitosis gene a)-related expressed kinase 3 // 8 Nek3 0.000103455 3.29166NM_199475 // Fam63a // family with sequence similarity 63, member A // 3|3 F2 // 75007 Fam63a 4.11E-07 3.29294NM_001290790 // Plcb2 // phospholipase C, beta 2 // 2 E5|2 59.43 cM // 18796 /// NM_177 Plcb2 5.50E-08 3.29899NM_201609 // Zfp652 // zinc finger protein 652 // 11 D|11 // 268469 /// ENSMUST00000091 Zfp652 1.76E-06 3.29936NM_018822 // Sgsh // N-sulfoglucosamine sulfohydrolase (sulfamidase) // 11 E2|11 83.36 Sgsh 3.97E-07 3.29967NM_183390 // Klhl6 // kelch-like 6 // 16 A3|16 // 239743 /// ENSMUST00000058839 // Klhl Klhl6 1.28E-05 3.30489NM_146008 // Tcp11l2 // t-complex 11 (mouse) like 2 // 10 C1|10 // 216198 /// ENSMUST00 Tcp11l2 0.000352699 3.30583NM_144812 // Tnrc6b // trinucleotide repeat containing 6b // 15 E1|15 // 213988 /// NM_ Tnrc6b 2.77E-05 3.30993--- 5.92E-05 3.31122NM_029654 // Atg2b // autophagy related 2B // 12 E|12 // 76559 /// ENSMUST00000041055 / Atg2b 1.96E-05 3.31361--- 0.00530807 3.3194NM_001285785 // Arhgap9 // Rho GTPase activating protein 9 // 10 D3|10 // 216445 /// NM Arhgap9 6.70E-07 3.32167NM_001004363 // Nuak1 // NUAK family, SNF1-like kinase, 1 // 10 C1|10 // 77976 /// ENSM Nuak1 0.00140047 3.32257NM_001026214 // Entpd5 // ectonucleoside triphosphate diphosphohydrolase 5 // 12 E|12 3 Entpd5 7.57E-08 3.32287ENSMUST00000126677 // Gm15537 // predicted gene 15537 // --- // --- Gm15537 4.42E-06 3.32418NM_001033352 // Klhl21 // kelch-like 21 // 4 E2|4 // 242785 /// ENSMUST00000097773 // K Klhl21 0.00013531 3.32954NM_019800 // Acp6 // acid phosphatase 6, lysophosphatidic // 3 F2.1|3 // 66659 /// XR_3 Acp6 3.62E-05 3.32989NM_009469 // Ulk1 // unc-51 like kinase 1 // 5|5 F // 22241 /// ENSMUST00000031490 // U Ulk1 2.62E-06 3.34077NM_172465 // Zdhhc9 // zinc finger, DHHC domain containing 9 // X A4|X // 208884 /// EN Zdhhc9 1.25E-07 3.34102NM_011937 // Gnpda1 // glucosamine-6-phosphate deaminase 1 // 18 B3|18 // 26384 /// ENS Gnpda1 7.23E-07 3.34973NM_001033167 // Slc22a23 // solute carrier family 22, member 23 // 13 A3.3|13 // 73102 Slc22a23 2.70E-05 3.35348NM_015786 // Hist1h1c // histone cluster 1, H1c // 13|13 A2-A3 // 50708 /// ENSMUST0000 Hist1h1c 6.36E-07 3.35635NM_001039511 // Ivns1abp // influenza virus NS1A binding protein // 1 G2|1 // 117198 // Ivns1abp 4.71E-07 3.35666NM_001164598 // Irf2bp2 // interferon regulatory factor 2 binding protein 2 // 8 E2|8 / Irf2bp2 1.30E-07 3.37045--- 0.00110064 3.38071NM_177184 // Vps13c // vacuolar protein sorting 13C (yeast) // 9 C|9 // 320528 /// ENSM Vps13c 3.47E-07 3.38381NM_019740 // Foxo3 // forkhead box O3 // 10 B2|10 22.79 cM // 56484 /// XR_380270 // LO Foxo3 1.28E-06 3.38702NM_133792 // Pla2g15 // phospholipase A2, group XV // 8 D3|8 // 192654 /// ENSMUST00000 Pla2g15 4.62E-08 3.38716NM_001163042 // Haus8 // 4HAUS augmin-like complex, subunit 8 // 8|8 C1 // 76478 /// NM Haus8 4.30E-05 3.39872NM_029436 // Klhl24 // kelch-like 24 // 16|16 B1 // 75785 /// ENSMUST00000023509 // Klh Klhl24 2.18E-05 3.40123NM_026192 // Calcoco1 // calcium binding and coiled coil domain 1 // 15 F3|15 // 67488 Calcoco1 7.48E-08 3.402NM_145588 // Kif22 // kinesin family member 22 // 7 F3|7 69.29 cM // 110033 /// ENSMUST Kif22 4.76E-05 3.42486--- 0.00157777 3.42734NM_029938 // H2afv // H2A histone family, member V // 11 A1|11 // 77605 /// ENSMUST0000 H2afv 1.30E-05 3.43182NM_001198789 // Ccpg1os // cell cycle progression 1, opposite strand // 9 D|9 // 546143 Ccpg1os 1.63E-08 3.4405NM_010568 // Insr // insulin receptor // 8 A1.1|8 1.82 cM // 16337 /// ENSMUST000000912 Insr 5.35E-06 3.44153NM_198308 // Pdpr // pyruvate dehydrogenase phosphatase regulatory subunit // 8 E1|8 // Pdpr 2.70E-06 3.44322NM_175445 // Rassf2 // Ras association (RalGDS/AF-6) domain family member 2 // 2 F2|2 / Rassf2 7.03E-08 3.44838NM_001252094 // Mettl20 // methyltransferase like 20 // 6 G3|6 // 320204 /// NM_0012520 Mettl20 0.000398718 3.47501NM_028149 // Fbxl20 // F-box and leucine-rich repeat protein 20 // 11 D|11 // 72194 /// Fbxl20 1.41E-06 3.48401NM_138745 // Mthfd1 // methylenetetrahydrofolate dehydrogenase (NADP+ dependent), methe Mthfd1 1.27E-05 3.48645NM_011906 // Tpra1 // transmembrane protein, adipocyte asscociated 1 // 6|6 D2 // 24100 Tpra1 4.84E-07 3.48998

NM_001184706 // Tfdp2 // transcription factor Dp 2 // 9 E3.3|9 // 211586 /// NM_0011847 Tfdp2 5.54E-05 3.49539NM_009213 // Smpd2 // sphingomyelin phosphodiesterase 2, neutral // 10 B2|10 // 20598 / Smpd2 7.75E-05 3.50305NM_001080746 // Gtf2i // general transcription factor II I // 5 G2|5 74.48 cM // 14886 Gtf2i 2.33E-05 3.50432NM_009274 // Srpk2 // serine/arginine-rich protein specific kinase 2 // 5 A3|5 10.36 cM Srpk2 5.39E-07 3.5044NM_010497 // Idh1 // isocitrate dehydrogenase 1 (NADP+), soluble // 1 C2|1 32.91 cM // Idh1 2.22E-08 3.517--- 0.00593002 3.519--- 0.00485474 3.52122NM_001163495 // Arhgap19 // Rho GTPase activating protein 19 // 19|19 D1 // 71085 /// N Arhgap19 0.00010112 3.52632NM_183276 // Nbeal2 // neurobeachin-like 2 // 9 F2|9 // 235627 /// ENSMUST00000133191 / Nbeal2 1.66E-07 3.52737NM_001163378 // 2700049A03Rik // RIKEN cDNA 2700049A03 gene // 12|12 C3 // 76967 /// NM 2700049A03Rik 8.07E-07 3.53809NM_029645 // Gatc // glutamyl-tRNA(Gln) amidotransferase, subunit C homolog (bacterial) Gatc 0.000102617 3.54044NM_177372 // Dna2 // DNA replication helicase 2 homolog (yeast) // 10 B4|10 // 327762 / Dna2 1.40E-07 3.5477NM_199197 // Rbfa // ribosome binding factor A // 18 E3|18 // 68731 /// ENSMUST00000025 Rbfa 0.000206571 3.55152AK159040 // 9130004J05Rik // RIKEN cDNA 9130004J05 gene // 15|15 // 71603 9130004J05Rik 0.00211247 3.56515--- 0.00630464 3.56993NM_207161 // Dnph1 // 2-deoxynucleoside 5-phosphate N-hydrolase 1 // 17 C|17 // 381101 Dnph1 0.000575852 3.58524NM_026599 // Cgnl1 // cingulin-like 1 // 9 D|9 // 68178 /// XM_006511395 // Cgnl1 // ci Cgnl1 4.72E-06 3.59088NM_031251 // Ctns // cystinosis, nephropathic // 11 B4|11 // 83429 /// XM_006534533 // Ctns 3.86E-07 3.59779NM_028048 // Slc25a35 // solute carrier family 25, member 35 // 11 B3|11 // 71998 /// E Slc25a35 7.18E-06 3.60054NM_001291190 // Ssh2 // slingshot homolog 2 (Drosophila) // 11 B5|11 // 237860 /// NM_1 Ssh2 8.34E-08 3.60084NM_153804 // Plekhg3 // pleckstrin homology domain containing, family G (with RhoGef do Plekhg3 6.81E-07 3.60759NM_001190320 // Clec4n // C-type lectin domain family 4, member n // 6 F3|6 58.3 cM // Clec4n 1.08E-07 3.61421NR_102275 // AI839979 // expressed sequence AI839979 // --- // 100740 AI839979 0.000995154 3.63358--- 1.48E-05 3.64526NR_037959 // 1600010M07Rik // RIKEN cDNA 1600010M07 gene // 7|7 // 69781 /// AK005418 / 1600010M07Ri 0.000365558 3.64917NM_025449 // Nicn1 // nicolin 1 // 9 F2|9 // 66257 /// ENSMUST00000035227 // Nicn1 // n Nicn1 9.66E-07 3.65175NM_001077696 // Hdac5 // histone deacetylase 5 // 11 D|11 // 15184 /// NM_001284248 // Hdac5 5.14E-07 3.65762XM_006506475 // Fam136a // family with sequence similarity 136, member A // 6 D1|6 // 6 Fam136a 0.000186046 3.66125ENSMUST00000075588 // Tnfrsf22 // tumor necrosis factor receptor superfamily, member 22 Tnfrsf22 0.000676646 3.67683NM_175337 // Mlh3 // mutL homolog 3 (E coli) // 12 D2|12 // 217716 /// ENSMUST000000193 Mlh3 0.000263422 3.67724NM_025807 // Slc16a9 // solute carrier family 16 (monocarboxylic acid transporters), me Slc16a9 2.51E-05 3.68395NM_174987 // Coa6 // cytochrome c oxidase assembly factor 6 // 8 E2|8 // 67892 /// ENSM Coa6 0.000359279 3.69077NM_026272 // Narf // nuclear prelamin A recognition factor // 11 E2|11 // 67608 /// ENS Narf 6.06E-06 3.69179--- 0.000664722 3.69439--- 0.00145151 3.70204NM_001167832 // Zfp764 // zinc finger protein 764 // 7 F3|7 // 233893 /// NM_146203 // Zfp764 4.41E-05 3.71639NR_046157 // Gm5086 // predicted gene 5086 // 13 D1|13 // 328314 Gm5086 5.40E-05 3.71742NM_024245 // Kif23 // kinesin family member 23 // 9 B|9 // 71819 /// ENSMUST00000034815 Kif23 0.00034265 3.74697NM_027534 // Kdsr // 3-ketodihydrosphingosine reductase // 1 E2.1|1 // 70750 /// XM_006 Kdsr 6.58E-06 3.75994NM_008856 // Prkch // protein kinase C, eta // 12|12 C3-D1 // 18755 /// ENSMUST00000021 Prkch 4.32E-07 3.7647NM_028995 // Nipal3 // NIPA-like domain containing 3 // 4 D3|4 // 74552 /// XM_00653922 Nipal3 1.06E-07 3.76616NM_197987 // Trim37 // tripartite motif-containing 37 // 11 C|11 // 68729 /// ENSMUST00 Trim37 6.71E-06 3.78131NM_008425 // Kcnj2 // potassium inwardly-rectifying channel, subfamily J, member 2 // 1 Kcnj2 0.000111591 3.78302NR_002864 // Peg13 // paternally expressed 13 // 15 D3|15 // 353342 Peg13 7.82E-07 3.7875NM_172693 // Galnt12 // UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactos Galnt12 0.0030931 3.80669NM_175128 // 4930430F08Rik // RIKEN cDNA 4930430F08 gene // 10 D1|10 // 68281 /// ENSMU 4930430F08Rik 0.00123909 3.80695NM_001163608 // Plxdc1 // plexin domain containing 1 // 11 D|11 // 72324 /// NM_028199 Plxdc1 2.50E-07 3.81808NM_019975 // Hacl1 // 2-hydroxyacyl-CoA lyase 1 // 14 B|14 // 56794 /// XM_006519320 // Hacl1 1.03E-06 3.82278NM_001083341 // Mboat2 // membrane bound O-acyltransferase domain containing 2 // 12 A1 Mboat2 0.000644177 3.83901--- 0.000984989 3.84583NM_027909 // C2cd2l // C2 calcium-dependent domain containing 2-like // 9|9 B // 71764 C2cd2l 6.46E-06 3.85243NM_011133 // Pole2 // polymerase (DNA directed), epsilon 2 (p59 subunit) // 12|12 C3 // Pole2 2.60E-07 3.87159NM_020270 // Scamp5 // secretory carrier membrane protein 5 // 9 B|9 // 56807 /// XM_00 Scamp5 9.52E-06 3.87484NM_016681 // Chek2 // checkpoint kinase 2 // 5 F|5 // 50883 /// XM_006535068 // Chek2 / Chek2 2.30E-06 3.87961NM_172681 // D930015E06Rik // RIKEN cDNA D930015E06 gene // 3 F1|3 // 229473 /// ENSMUS D930015E06Rik 1.90E-06 3.89911NM_001033393 // Tmem104 // transmembrane protein 104 // 11 E2|11 // 320534 /// ENSMUST0 Tmem104 2.91E-06 3.90125ENSMUST00000086363 // Tmem150b // transmembrane protein 150B // 7 A1|7 // 330460 /// NM Tmem150b 1.01E-05 3.9061NM_001164099 // Add3 // adducin 3 (gamma) // 19 D2|19 47.18 cM // 27360 /// NM_00116410 Add3 1.98E-05 3.91505NM_170758 // Cd300a // CD300A antigen // 11 E2|11 80.54 cM // 217303 /// XM_006533069 / Cd300a 5.15E-07 3.92312NM_001113283 // Fam214a // family with sequence similarity 214, member A // 9 D|9 // 23 Fam214a 7.32E-08 3.92481NM_153542 // Lrrc20 // leucine rich repeat containing 20 // 10 B4|10 // 216011 /// ENSM Lrrc20 1.30E-07 3.92634NM_052976 // Ophn1 // oligophrenin 1 // X|X C2 // 94190 /// ENSMUST00000033560 // Ophn1 Ophn1 4.71E-08 3.92734NM_001163760 // 6430548M08Rik // RIKEN cDNA 6430548M08 gene // 8 E1|8 // 234797 /// NM_ 6430548M08Ri 1.58E-06 3.92969NM_146094 // Fads1 // fatty acid desaturase 1 // 19 A|19 // 76267 /// ENSMUST0000001080 Fads1 2.30E-10 3.93208NM_010658 // Mafb // v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B ( Mafb 1.06E-08 3.93776NM_145475 // Cerk // ceramide kinase // 15 E2|15 // 223753 /// ENSMUST00000044332 // Ce Cerk 5.32E-08 3.95543NM_001145960 // Slc37a2 // solute carrier family 37 (glycerol-3-phosphate transporter), Slc37a2 1.51E-07 3.96226NM_028894 // Lonrf3 // LON peptidase N-terminal domain and ring finger 3 // X|X A2 // 7 Lonrf3 2.13E-06 3.98212--- 0.00276685 4.00083--- 0.000521207 4.00732NM_001001806 // Zfp36l2 // zinc finger protein 36, C3H type-like 2 // 17 E4|17 // 12193 Zfp36l2 3.50E-08 4.01703--- 0.00206897 4.0495NM_020567 // Gmnn // geminin // 13 A3.1|13 // 57441 /// XM_006516722 // Gmnn // geminin Gmnn 3.28E-05 4.05904NM_001081128 // Mtr // 5-methyltetrahydrofolate-homocysteine methyltransferase // 13 A1 Mtr 2.14E-05 4.06568NM_172134 // Pdxk // pyridoxal (pyridoxine, vitamin B6) kinase // 10 C1|10 39.72 cM // Pdxk 4.06E-07 4.06933NM_024184 // Asf1b // anti-silencing function 1B histone chaperone // 8 C3|8 // 66929 / Asf1b 0.00109549 4.08832NM_001142701 // Hmha1 // histocompatibility (minor) HA-1 // 10 C1|10 // 70719 /// NM_02 Hmha1 4.66E-07 4.08964--- 0.00560658 4.1452NM_133765 // Fbxo31 // F-box protein 31 // 8 E1|8 // 76454 /// ENSMUST00000059018 // Fb Fbxo31 6.84E-07 4.16675NM_001289895 // Tns1 // tensin 1 // 1 C3|1 38.17 cM // 21961 /// NM_027884 // Tns1 // t Tns1 7.06E-08 4.17112NM_016974 // Dbp // D site albumin promoter binding protein // 7 B4|7 29.45 cM // 13170 Dbp 1.51E-05 4.18229NM_173442 // Gcnt1 // glucosaminyl (N-acetyl) transferase 1, core 2 // 19 B|19 12.75 cM Gcnt1 3.05E-06 4.18656NM_001079686 // Syne1 // spectrin repeat containing, nuclear envelope 1 // 10 A1|10 // Syne1 1.91E-05 4.19033NM_018789 // Foxo4 // forkhead box O4 // X C3-D|X 43.89 cM // 54601 /// ENSMUST00000062 Foxo4 0.00140243 4.19144NM_178589 // Tnfrsf21 // tumor necrosis factor receptor superfamily, member 21 // 17|17 Tnfrsf21 6.53E-09 4.202NM_001276292 // Wwp1 // WW domain containing E3 ubiquitin protein ligase 1 // 4 A3|4 // Wwp1 2.19E-09 4.22519ENSMUST00000104480 // Gm26143 // predicted gene, 26143 // --- // --- Gm26143 8.04E-06 4.23445NM_146040 // Cdca7l // cell division cycle associated 7 like // 12 F2|12 // 217946 /// Cdca7l 6.31E-05 4.25859--- 0.00171893 4.27098NM_001081176 // Polr3g // polymerase (RNA) III (DNA directed) polypeptide G // 13 C3|13 Polr3g 3.05E-08 4.28052--- 7.81E-06 4.31809NM_016917 // Slc40a1 // solute carrier family 40 (iron-regulated transporter), member 1 Slc40a1 6.34E-09 4.31818--- 0.00589373 4.3215

NM_008628 // Msh2 // mutS homolog 2 (E. coli) // 17 E4|17 57.87 cM // 17685 /// ENSMUST Msh2 3.35E-05 4.33216NM_028964 // Snx29 // sorting nexin 29 // --- // 74478 /// ENSMUST00000122168 // Snx29 Snx29 5.93E-05 4.35445NM_012006 // Acot1 // acyl-CoA thioesterase 1 // 12 D1|12 39.0 cM // 26897 /// ENSMUST0 Acot1 0.000801152 4.36034NM_001099738 // Dnajc28 // DnaJ (Hsp40) homolog, subfamily C, member 28 // 16 C3.3|16 / Dnajc28 0.000138227 4.3736NM_001081326 // Agl // amylo-1,6-glucosidase, 4-alpha-glucanotransferase // 3 G1|3 // 7 Agl 3.01E-05 4.37535NM_172468 // Snx30 // sorting nexin family member 30 // 4 B3|4 // 209131 /// ENSMUST000 Snx30 2.42E-08 4.44061NM_001161763 // Fmo5 // flavin containing monooxygenase 5 // 3 F2.2|3 // 14263 /// NM_0 Fmo5 3.45E-06 4.44519NM_011159 // Prkdc // protein kinase, DNA activated, catalytic polypeptide // 16 10.09 Prkdc 6.59E-07 4.49516--- 0.000103766 4.51287NM_001190297 // Gpr155 // G protein-coupled receptor 155 // 2 C3|2 // 68526 /// NM_0012 Gpr155 2.68E-05 4.52691NM_001130412 // Lpin1 // lipin 1 // 12 A1.1|12 7.9 cM // 14245 /// NM_015763 // Lpin1 / Lpin1 2.90E-05 4.56102ENSMUST00000180988 // Gm26912 // predicted gene, 26912 // --- // --- Gm26912 9.49E-05 4.5685NM_001081396 // Tbc1d31 // TBC1 domain family, member 31 // 15 D1|15 // 210544 /// NM_0 Tbc1d31 6.20E-07 4.58111NM_172771 // Dmxl2 // Dmx-like 2 // 9|9 C // 235380 /// ENSMUST00000118163 // Dmxl2 // Dmxl2 3.97E-07 4.59891NM_027491 // Rragd // Ras-related GTP binding D // 4 A5|4 14.57 cM // 52187 /// ENSMUST Rragd 3.81E-06 4.60999NM_029482 // 4930579G24Rik // RIKEN cDNA 4930579G24 gene // 3|3 F1 // 75939 /// ENSMUST 4930579G24Rik 0.000134984 4.61866NM_177337 // Arl11 // ADP-ribosylation factor-like 11 // 14 D1|14 // 219144 /// XM_0065 Arl11 9.73E-08 4.62287NM_021310 // Jmy // junction-mediating and regulatory protein // 13 C3|13 // 57748 /// Jmy 9.69E-08 4.63693--- 0.000859953 4.65945NM_175645 // Xylt1 // xylosyltransferase 1 // 7 F2|7 // 233781 /// ENSMUST00000032892 / Xylt1 2.23E-06 4.67984NM_028340 // Susd3 // sushi domain containing 3 // 13|13 B1 // 66329 /// XM_006516941 / Susd3 5.93E-05 4.68245NM_001005341 // Ypel2 // yippee-like 2 (Drosophila) // 11 C|11 // 77864 /// ENSMUST0000 Ypel2 5.05E-06 4.7203NM_009025 // Rasa3 // RAS p21 protein activator 3 // 8 A1.1|8 6.29 cM // 19414 /// XM_0 Rasa3 1.44E-07 4.73008NM_145938 // Rpp40 // ribonuclease P 40 subunit // 13 A3.3|13 // 208366 /// XM_00651663 Rpp40 0.000108259 4.73663NM_183031 // Gpr183 // G protein-coupled receptor 183 // 14 E5|14 // 321019 /// ENSMUST Gpr183 2.36E-07 4.74425NM_001163268 // Lpar5 // lysophosphatidic acid receptor 5 // 6 F2|6 // 381810 /// ENSMU Lpar5 0.000494173 4.75517NM_029091 // Klc4 // kinesin light chain 4 // 17 C|17 // 74764 /// XM_006525042 // Klc4 Klc4 9.95E-06 4.79101NM_134188 // Acot2 // acyl-CoA thioesterase 2 // 12|12 D3 // 171210 /// ENSMUST00000021 Acot2 7.76E-06 4.81287NM_001170694 // Rcbtb2 // regulator of chromosome condensation (RCC1) and BTB (POZ) dom Rcbtb2 4.36E-07 4.83057NM_146073 // Zdhhc14 // zinc finger, DHHC domain containing 14 // 17 A1|17 // 224454 // Zdhhc14 2.30E-07 4.83978NM_133898 // N4bp2l1 // NEDD4 binding protein 2-like 1 // 5 G3|5 // 100637 /// ENSMUST0 N4bp2l1 9.55E-07 4.84271--- 0.00250987 4.84813--- 0.00648934 4.88267XM_006527412 // Rab3il1 // RAB3A interacting protein (rabin3)-like 1 // 19 A|19 // 7476 Rab3il1 4.10E-08 4.88372--- 0.00255325 4.88429NM_181401 // Tmem64 // transmembrane protein 64 // 4 A2|4 // 100201 /// ENSMUST00000062 Tmem64 1.48E-07 4.88689NM_001270537 // Bin2 // bridging integrator 2 // 15 F1|15 // 668218 /// ENSMUST00000182 Bin2 6.31E-07 4.8884--- 9.67E-06 4.89615NM_177231 // Arrb1 // arrestin, beta 1 // 7 E2|7 54.09 cM // 109689 /// NM_178220 // Ar Arrb1 5.13E-10 4.91596NM_001042591 // Arrdc3 // arrestin domain containing 3 // 13 C3|13 // 105171 /// XM_006 Arrdc3 5.52E-09 4.93264NM_008115 // Gfra2 // glial cell line derived neurotrophic factor family receptor alpha Gfra2 5.13E-07 4.94602NM_028372 // Mblac2 // metallo-beta-lactamase domain containing 2 // 13 C3|13 // 72852 Mblac2 9.91E-08 4.99099--- 0.00660571 4.99192NM_030251 // Abtb1 // ankyrin repeat and BTB (POZ) domain containing 1 // 6 D1|6 // 802 Abtb1 8.50E-07 4.99214NM_145220 // Appl2 // adaptor protein, phosphotyrosine interaction, PH domain and leuci Appl2 9.50E-07 5.00186NM_027872 // Slc46a3 // solute carrier family 46, member 3 // 5 G3|5 // 71706 /// XM_00 Slc46a3 2.17E-07 5.01576NM_033602 // Peli2 // pellino 2 // 14 C1|14 24.6 cM // 93834 /// XM_006519740 // Peli2 Peli2 2.48E-06 5.0211--- 0.000858014 5.02348NM_009128 // Scd2 // stearoyl-Coenzyme A desaturase 2 // 19 C3|19 37.98 cM // 20250 /// Scd2 7.40E-11 5.04277--- 0.00298249 5.05527--- 0.00298692 5.06922NM_177000 // C130050O18Rik // RIKEN cDNA C130050O18 gene // 5 G2|5 // 319772 /// ENSMUS C130050O18Rik 0.00023376 5.10769NM_009987 // Cx3cr1 // chemokine (C-X3-C motif) receptor 1 // 9 F4|9 // 13051 /// ENSMU Cx3cr1 1.45E-06 5.14486ENSMUST00000083115 // Gm24041 // predicted gene, 24041 // --- // --- Gm24041 0.000118076 5.15411--- 0.00465442 5.16962NM_010753 // Mxd4 // Max dimerization protein 4 // 5 B2|5 17.84 cM // 17122 /// ENSMUST Mxd4 3.32E-05 5.19344NM_001168491 // Pdcd4 // programmed cell death 4 // 19 D2|19 48.73 cM // 18569 /// NM_0 Pdcd4 1.40E-06 5.19504--- 0.00396414 5.29807NM_001289740 // Mturn // maturin, neural progenitor differentiation regulator homolog ( Mturn 2.18E-07 5.30842--- 0.00197267 5.32397NM_176837 // Arhgap18 // Rho GTPase activating protein 18 // 10 A4|10 // 73910 /// XM_0 Arhgap18 3.01E-08 5.35785NM_138956 // Rassf3 // Ras association (RalGDS/AF-6) domain family member 3 // 10 D2|10 Rassf3 2.36E-07 5.39814NM_001033257 // Phactr2 // phosphatase and actin regulator 2 // 10 A2|10 // 215789 /// Phactr2 2.64E-06 5.40635NM_023326 // Bmyc // brain expressed myelocytomatosis oncogene // 2 A3|2 // 107771 /// Bmyc 7.81E-06 5.4613NM_145401 // Prkag2 // protein kinase, AMP-activated, gamma 2 non-catalytic subunit // Prkag2 5.82E-08 5.46539NM_145853 // Tpcn1 // two pore channel 1 // 5 F|5 // 252972 /// ENSMUST00000046426 // T Tpcn1 0.00012439 5.46886--- 0.000482856 5.47171NM_001199105 // Trp53inp1 // transformation related protein 53 inducible nuclear protei Trp53inp1 2.60E-07 5.47272ENSMUST00000150912 // Stard9 // START domain containing 9 // 2 E5|2 // 668880 /// ENSMU Stard9 1.99E-07 5.53742NM_172514 // Tmem71 // transmembrane protein 71 // 15 D2|15 // 213068 /// ENSMUST000000 Tmem71 7.69E-07 5.62653--- 0.00203752 5.66189NM_018775 // Tbc1d8 // TBC1 domain family, member 8 // 1 B|1 // 54610 /// XM_006496146 Tbc1d8 3.96E-08 5.73607--- 0.00210668 5.77001NM_001287514 // Cebpa // CCAAT/enhancer binding protein (C/EBP), alpha // 7 B1|7 21.02 Cebpa 6.24E-08 5.78863--- 4.38E-05 5.90715--- 0.00149403 6.02617NM_001170643 // Rnf144b // ring finger protein 144B // 13 A5|13 // 218215 /// NM_146042 Rnf144b 2.15E-07 6.09794NM_001271413 // Nfam1 // Nfat activating molecule with ITAM motif 1 // 15|15 E2 // 7403 Nfam1 9.53E-08 6.12583NM_198664 // Tbc1d2 // TBC1 domain family, member 2 // 4 B1|4 // 381605 /// ENSMUST0000 Tbc1d2 6.30E-06 6.21982NM_021462 // Mknk2 // MAP kinase-interacting serine/threonine kinase 2 // 10 C1|10 // 1 Mknk2 4.31E-07 6.24005NM_026436 // Tmem86a // transmembrane protein 86A // 7 B4|7 // 67893 /// ENSMUST0000001 Tmem86a 7.76E-07 6.30914NM_001146180 // Mtss1 // metastasis suppressor 1 // 15 D1|15 // 211401 /// NM_144800 // Mtss1 6.98E-09 6.44171--- 6.51E-07 6.53994NM_199221 // Cd300lb // CD300 antigen like family member B // 11 E2|11 // 217304 /// EN Cd300lb 1.54E-09 6.60477NR_030718 // F630028O10Rik // RIKEN cDNA F630028O10 gene // X C3|X // 100038363 /// ENS F630028O10Rik 7.40E-07 6.63335NM_009128 // Scd2 // stearoyl-Coenzyme A desaturase 2 // 19 C3|19 37.98 cM // 20250 /// Scd2 1.40E-07 6.69929--- 0.00067707 6.89075--- 1.22E-06 6.89436NM_001013370 // Sesn1 // sestrin 1 // 10 B2|10 22.77 cM // 140742 /// NM_001162908 // S Sesn1 2.72E-07 6.90316--- 4.11E-05 6.93345--- 0.000974395 7.52172NM_001242423 // Fam105a // family with sequence similarity 105, member A // 15 B1|15 // Fam105a 1.04E-07 7.726NM_026189 // Eepd1 // endonuclease/exonuclease/phosphatase family domain containing 1 / Eepd1 1.60E-08 8.076

XM_006500510 // Stard9 // START domain containing 9 // 2 E5|2 // 668880 /// ENSMUST0000 Stard9 1.28E-07 8.30015NM_175930 // Rapgef5 // Rap guanine nucleotide exchange factor (GEF) 5 // 12 F2|12 // 2 Rapgef5 1.35E-09 8.30471NM_001252506 // St6gal1 // beta galactoside alpha 2,6 sialyltransferase 1 // 16 B1|16 1 St6gal1 8.62E-08 8.45208NM_009924 // Cnr2 // cannabinoid receptor 2 (macrophage) // 4 D3|4 // 12802 /// ENSMUST Cnr2 8.69E-07 8.47887NM_008535 // Lyl1 // lymphoblastomic leukemia 1 // 8 C3|8 41.02 cM // 17095 /// ENSMUST Lyl1 1.23E-07 8.69163ENSMUST00000106357 // Ypel3 // yippee-like 3 (Drosophila) // 7 F3|7 // 66090 /// NM_025 Ypel3 5.99E-08 8.77434--- 0.000235818 8.90352--- 0.000594544 8.93783ENSMUST00000170967 // Rb1 // retinoblastoma 1 // 14 D3|14 38.73 cM // 19645 Rb1 3.61E-06 9.18381--- 7.61E-06 10.3889--- 0.00512012 10.818NM_175116 // Lpar6 // lysophosphatidic acid receptor 6 // 14 D3|14 // 67168 /// ENSMUST Lpar6 5.68E-10 11.0058--- 3.69E-05 12.518NM_001039484 // Kcnj10 // potassium inwardly-rectifying channel, subfamily J, member 10 Kcnj10 1.50E-06 13.4457NM_009911 // Cxcr4 // chemokine (C-X-C motif) receptor 4 // 1 E4|1 56.43 cM // 12767 // Cxcr4 2.50E-09 14.8111NM_011994 // Abcd2 // ATP-binding cassette, sub-family D (ALD), member 2 // 15 E-F|15 / Abcd2 1.27E-08 27.5266

gene_assignment Gene Symbol p-value(24h HDM/LPS vs. 24h LPS) Fold-Change(24h HDM/LPS vs. 24h LPS)NM_008625 // Mrc1 // mannose receptor, C type 1 // 2 A2|2 10.46 cM // 17533 /// ENSMUST Mrc1 1.52E-09 19.1231NM_177909 // Slc9a9 // solute carrier family 9 (sodium/hydrogen exchanger), member 9 // Slc9a9 1.20E-08 17.6318NM_147220 // Abca9 // ATP-binding cassette, sub-family A (ABC1), member 9 // 11 E1|11 / Abca9 1.23E-09 16.8219NR_030718 // F630028O10Rik // RIKEN cDNA F630028O10 gene // X C3|X // 100038363 /// ENS F630028O10Rik 3.87E-08 15.8444NM_011638 // Tfrc // transferrin receptor // 16 B3|16 23.06 cM // 22042 /// ENSMUST0000 Tfrc 2.01E-11 15.5247XM_006504587 // Nxpe5 // neurexophilin and PC-esterase domain family, member 5 // 5 G2| Nxpe5 4.60E-07 13.2704NM_001204252 // Clec10a // C-type lectin domain family 10, member A // 11 B3|11 42.99 c Clec10a 2.38E-06 13.1808NM_007642 // Cd28 // CD28 antigen // 1 C1-C3|1 30.52 cM // 12487 /// ENSMUST00000027165 Cd28 7.70E-08 12.6421NR_046157 // Gm5086 // predicted gene 5086 // 13 D1|13 // 328314 Gm5086 4.70E-07 11.8449NM_139138 // Emr4 // EGF-like module containing, mucin-like, hormone receptor-like sequ Emr4 1.26E-06 11.3012ENSMUST00000103426 // Ighm // immunoglobulin heavy constant mu // --- // --- /// ENSMUS Ighm 1.36E-09 10.5823NM_010517 // Igfbp4 // insulin-like growth factor binding protein 4 // 11 D|11 // 16010 Igfbp4 7.13E-09 10.5244NM_009888 // Cfh // complement component factor h // 1 F|1 61.62 cM // 12628 /// ENSMUS Cfh 2.91E-10 9.88262NM_001013370 // Sesn1 // sestrin 1 // 10 B2|10 22.77 cM // 140742 /// NM_001162908 // S Sesn1 7.23E-08 9.867NM_001037937 // Deptor // DEP domain containing MTOR-interacting protein // 15 D1|15 21 Deptor 1.96E-07 9.59837NM_001252530 // Slco2b1 // solute carrier organic anion transporter family, member 2b1 Slco2b1 7.76E-06 9.12333NM_008611 // Mmp8 // matrix metallopeptidase 8 // 9 A1|9 // 17394 /// ENSMUST0000001876 Mmp8 2.05E-07 8.79564NM_029861 // Cnrip1 // cannabinoid receptor interacting protein 1 // 11|11 A3.1 // 3806 Cnrip1 1.18E-06 8.5377--- 0.00321704 8.44661NM_001130412 // Lpin1 // lipin 1 // 12 A1.1|12 7.9 cM // 14245 /// NM_015763 // Lpin1 / Lpin1 2.39E-06 8.34154NM_001252506 // St6gal1 // beta galactoside alpha 2,6 sialyltransferase 1 // 16 B1|16 1 St6gal1 9.37E-08 8.26156NM_001163495 // Arhgap19 // Rho GTPase activating protein 19 // 19|19 D1 // 71085 /// N Arhgap19 2.29E-06 8.24015NM_020008 // Clec7a // C-type lectin domain family 7, member a // 6 F3|6 // 56644 /// E Clec7a 5.11E-11 8.2215--- 8.13E-05 8.21069NM_001289740 // Mturn // maturin, neural progenitor differentiation regulator homolog ( Mturn 3.86E-08 8.02225NM_134066 // Akr1c18 // aldo-keto reductase family 1, member C18 // 13 A1|13 // 105349 Akr1c18 2.82E-06 7.74736NM_001081278 // Tbc1d4 // TBC1 domain family, member 4 // 14 E2.3|14 // 210789 /// XM_0 Tbc1d4 1.15E-07 7.65743NM_001037937 // Deptor // DEP domain containing MTOR-interacting protein // 15 D1|15 21 Deptor 2.00E-06 7.59874NM_001039484 // Kcnj10 // potassium inwardly-rectifying channel, subfamily J, member 10 Kcnj10 9.94E-06 7.56097NM_133670 // Sult1a1 // sulfotransferase family 1A, phenol-preferring, member 1 // 7 F3 Sult1a1 6.07E-08 7.52235NM_016917 // Slc40a1 // solute carrier family 40 (iron-regulated transporter), member 1 Slc40a1 5.32E-10 7.38236NM_177715 // Kctd12 // potassium channel tetramerisation domain containing 12 // 14 E2. Kctd12 3.92E-09 7.02918--- 0.000962486 6.7899NM_001166493 // Rasgrp3 // RAS, guanyl releasing protein 3 // 17 E2|17 // 240168 /// NM Rasgrp3 1.41E-08 6.73383NM_146008 // Tcp11l2 // t-complex 11 (mouse) like 2 // 10 C1|10 // 216198 /// ENSMUST00 Tcp11l2 1.33E-05 6.69417--- 0.00131646 6.67493NM_025285 // Stmn2 // stathmin-like 2 // 3 A1|3 2.15 cM // 20257 /// ENSMUST00000029002 Stmn2 2.06E-06 6.58946--- 0.000457687 6.3865NM_007420 // Adrb2 // adrenergic receptor, beta 2 // 18 E1|18 35.1 cM // 11555 /// ENSM Adrb2 1.25E-05 6.37003NM_008830 // Abcb4 // ATP-binding cassette, sub-family B (MDR/TAP), member 4 // 5 A1|5 Abcb4 3.09E-11 6.30977NM_010016 // Cd55 // CD55 antigen // 1 E4|1 56.89 cM // 13136 /// XM_006529117 // Cd55 Cd55 3.86E-06 6.30499NM_001190297 // Gpr155 // G protein-coupled receptor 155 // 2 C3|2 // 68526 /// NM_0012 Gpr155 6.64E-06 6.19065ENSMUST00000103607 // Trav13d-4 // T cell receptor alpha variable 13D-4 // --- // --- Trav13d-4 1.43E-05 5.88149NM_001252578 // Sulf2 // sulfatase 2 // 2 H3|2 // 72043 /// NM_001252579 // Sulf2 // su Sulf2 2.91E-08 5.78565NM_001170694 // Rcbtb2 // regulator of chromosome condensation (RCC1) and BTB (POZ) dom Rcbtb2 1.88E-07 5.78306NM_181401 // Tmem64 // transmembrane protein 64 // 4 A2|4 // 100201 /// ENSMUST00000062 Tmem64 6.89E-08 5.7533NM_001168491 // Pdcd4 // programmed cell death 4 // 19 D2|19 48.73 cM // 18569 /// NM_0 Pdcd4 9.24E-07 5.69773NM_172903 // Man2a2 // mannosidase 2, alpha 2 // 7 D2|7 // 140481 /// ENSMUST0000009834 Man2a2 4.95E-10 5.67678NM_001033872 // Smagp // small cell adhesion glycoprotein // 15 F1|15 // 207818 /// NM_ Smagp 3.40E-06 5.66391NM_001290633 // Reps2 // RALBP1 associated Eps domain containing protein 2 // X F4|X // Reps2 4.30E-08 5.61896NM_001276292 // Wwp1 // WW domain containing E3 ubiquitin protein ligase 1 // 4 A3|4 // Wwp1 5.45E-10 5.56734NM_001030289 // Mmp27 // matrix metallopeptidase 27 // 9 A1|9 // 234911 /// XM_00650985 Mmp27 4.59E-09 5.52372NR_028534 // Snord88c // small nucleolar RNA, C/D box 88C // 7|7 // 100217434 /// ENSMU Snord88c 0.00240412 5.50916NM_177378 // Rnf150 // ring finger protein 150 // 8 C2|8 // 330812 /// ENSMUST000000785 Rnf150 8.62E-07 5.46237NM_019521 // Gas6 // growth arrest specific 6 // 8 A1.1|8 6.06 cM // 14456 /// ENSMUST0 Gas6 3.90E-10 5.3999NM_001159745 // St8sia4 // ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 4 St8sia4 4.61E-09 5.35003--- 0.00481451 5.34074--- 0.000429354 5.21336NM_008548 // Man1a // mannosidase 1, alpha // 10 B3|10 // 17155 /// ENSMUST00000003843 Man1a 1.08E-08 5.19652--- 0.00538369 5.19257--- 0.00186282 5.18253--- 0.00392971 5.14156NM_027872 // Slc46a3 // solute carrier family 46, member 3 // 5 G3|5 // 71706 /// XM_00 Slc46a3 1.98E-07 5.11488NM_001113386 // Lifr // leukemia inhibitory factor receptor // 15 A1|15 3.46 cM // 1688 Lifr 3.75E-06 5.11004NM_009194 // Slc12a2 // solute carrier family 12, member 2 // 18 D3|18 32.15 cM // 2049 Slc12a2 3.99E-07 5.07062NM_026790 // Ifi27 // interferon, alpha-inducible protein 27 // 12 E|12 52.93 cM // 526 Ifi27 1.69E-06 5.0342AK143703 // Gm19422 // predicted gene, 19422 // 14|14 50.9 cM // 100502869 /// XM_00651 Gm19422 2.06E-05 5.00368NM_001166391 // F13a1 // coagulation factor XIII, A1 subunit // 13 A3.3|13 // 74145 /// F13a1 1.69E-07 4.96518NM_028390 // Anln // anillin, actin binding protein // 9|9 A4 // 68743 /// XM_006510581 Anln 2.36E-05 4.93853--- 0.00353509 4.93149NM_177353 // Slc9a7 // solute carrier family 9 (sodium/hydrogen exchanger), member 7 // Slc9a7 3.31E-07 4.91369NM_027363 // Chp2 // calcineurin-like EF hand protein 2 // 7|7 F3 // 70261 /// ENSMUST0 Chp2 1.93E-05 4.89503ENSMUST00000139492 // Gm13710 // predicted gene 13710 // 2 D|2 // 672763 Gm13710 3.57E-05 4.86672NM_001170333 // Clec4a2 // C-type lectin domain family 4, member a2 // 6 F3|6 58.18 cM Clec4a2 3.42E-06 4.8594NM_008969 // Ptgs1 // prostaglandin-endoperoxide synthase 1 // 2 B|2 24.19 cM // 19224 Ptgs1 4.18E-08 4.84567NM_027343 // Cd209g // CD209g antigen // 8 A1.1|8 // 70192 /// ENSMUST00000130372 // Cd Cd209g 2.30E-06 4.76302NM_175406 // Atp6v0d2 // ATPase, H+ transporting, lysosomal V0 subunit D2 // 4 A3|4 // Atp6v0d2 8.79E-09 4.71221NM_001146031 // Nrcam // neuron-glia-CAM-related cell adhesion molecule // 12 B3|12 20. Nrcam 6.68E-05 4.7093ENSMUST00000090986 // Fcrls // Fc receptor-like S, scavenger receptor // 3 F1|3 // 8089 Fcrls 3.38E-08 4.70319AK132205 // Gm10554 // predicted gene 10554 // 18 A1|18 // 100038541 Gm10554 0.000102191 4.68893NM_011075 // Abcb1b // ATP-binding cassette, sub-family B (MDR/TAP), member 1B // 5 A1| Abcb1b 5.61E-05 4.67575NM_010753 // Mxd4 // Max dimerization protein 4 // 5 B2|5 17.84 cM // 17122 /// ENSMUST Mxd4 5.44E-05 4.65655NM_025877 // Slc25a23 // solute carrier family 25 (mitochondrial carrier; phosphate car Slc25a23 2.54E-07 4.59158--- 0.0012773 4.58457--- 0.00480842 4.57555NM_010740 // Cd93 // CD93 antigen // 2 G3|2 73.48 cM // 17064 /// ENSMUST00000099269 // Cd93 2.34E-08 4.57366NM_009139 // Ccl6 // chemokine (C-C motif) ligand 6 // 11 C|11 50.85 cM // 20305 /// EN Ccl6 6.19E-08 4.52214NM_175366 // Mex3b // mex3 homolog B (C. elegans) // 7 D3|7 47.35 cM // 108797 /// ENSM Mex3b 1.81E-05 4.49269NM_001081204 // B3glct // beta-3-glucosyltransferase // 5 G3|5 // 381694 /// ENSMUST000 B3glct 1.54E-05 4.47304NM_007913 // Egr1 // early growth response 1 // 18 C/D|18 18.76 cM // 13653 /// ENSMUST Egr1 1.36E-05 4.45971--- 0.00388425 4.45467NM_001113283 // Fam214a // family with sequence similarity 214, member A // 9 D|9 // 23 Fam214a 3.74E-08 4.43545NM_011173 // Pros1 // protein S (alpha) // 16 C1.3|16 // 19128 /// ENSMUST00000023629 / Pros1 3.06E-06 4.36093NM_010444 // Nr4a1 // nuclear receptor subfamily 4, group A, member 1 // 15|15 F // 153 Nr4a1 1.39E-07 4.34979

NM_008043 // Frat1 // frequently rearranged in advanced T cell lymphomas // 19 C3|19 35 Frat1 7.88E-05 4.34905ENSMUST00000083940 // Gm25683 // predicted gene, 25683 // --- // --- Gm25683 0.000160423 4.34073ENSMUST00000104390 // Gm25631 // predicted gene, 25631 // --- // --- Gm25631 0.00039016 4.33519NM_024264 // Cyp27a1 // cytochrome P450, family 27, subfamily a, polypeptide 1 // 1 C3| Cyp27a1 6.87E-07 4.32338--- 0.00429966 4.30894--- 0.00429966 4.30894ENSMUST00000157983 // Gm24186 // predicted gene, 24186 // --- // --- Gm24186 0.00438887 4.30532NM_011994 // Abcd2 // ATP-binding cassette, sub-family D (ALD), member 2 // 15 E-F|15 / Abcd2 7.40E-06 4.29056NM_001242423 // Fam105a // family with sequence similarity 105, member A // 15 B1|15 // Fam105a 1.51E-06 4.2547AK047378 // Chst10 // carbohydrate sulfotransferase 10 // 1 B|1 // 98388 /// NM_145142 Chst10 1.42E-05 4.24565--- 0.00331374 4.23619NM_176837 // Arhgap18 // Rho GTPase activating protein 18 // 10 A4|10 // 73910 /// XM_0 Arhgap18 9.86E-08 4.23322--- 0.000590043 4.23298NM_011311 // S100a4 // S100 calcium binding protein A4 // 3 F1-F2|3 39.27 cM // 20198 / S100a4 0.000115173 4.21562--- 0.000477863 4.21078NR_029535 // Mir99a // microRNA 99a // 16|16 // 387229 /// ENSMUST00000083596 // Mir99a Mir99a 0.000145776 4.19467--- 0.000972229 4.18512NM_001289458 // Hgf // hepatocyte growth factor // 5 A2-A3|5 7.07 cM // 15234 /// NM_00 Hgf 7.59E-07 4.18453NM_174857 // Mamdc2 // MAM domain containing 2 // 19 B|19 // 71738 /// XM_006527345 // Mamdc2 6.48E-07 4.1777--- 0.0040638 4.14685AK032971 // Gm11974 // predicted gene 11974 // 11 A1|11 // 100041286 Gm11974 0.000918128 4.10122NM_001184706 // Tfdp2 // transcription factor Dp 2 // 9 E3.3|9 // 211586 /// NM_0011847 Tfdp2 2.44E-05 4.06039--- 0.00134847 4.05465NM_001127330 // Pparg // peroxisome proliferator activated receptor gamma // 6 E3-F1|6 Pparg 1.62E-08 4.02496AK136317 // Gm19816 // predicted gene, 19816 // 3 E1|3 29.17 cM // 100503654 Gm19816 0.000292668 4.00666NM_001101656 // Gm11710 // predicted gene 11710 // 11 E2|11 // 100043123 /// NM_0011016 Gm11710 6.89E-09 3.98269NM_133977 // Trf // transferrin // 9 F1-F3|9 55.03 cM // 22041 /// ENSMUST00000035158 / Trf 2.81E-09 3.98004NM_020332 // Ank // progressive ankylosis // 15 B1|15 10.23 cM // 11732 /// ENSMUST0000 Ank 1.28E-07 3.97919NM_001198570 // Abi2 // abl-interactor 2 // 1 C2|1 // 329165 /// NM_001198571 // Abi2 / Abi2 1.01E-05 3.96162--- 0.00252677 3.94724ENSMUST00000141541 // Gm15503 // predicted gene 15503 // --- // --- /// XM_006508140 // Gm15503 8.29E-06 3.941NM_010513 // Igf1r // insulin-like growth factor I receptor // 7 D1|7 37.27 cM // 16001 Igf1r 3.71E-07 3.93858--- 0.00352524 3.93815--- 0.000904224 3.91254NM_008008 // Fgf7 // fibroblast growth factor 7 // 2|2 F-G // 14178 /// ENSMUST00000064 Fgf7 5.06E-07 3.8733NM_001002268 // Gpr126 // G protein-coupled receptor 126 // 10 A2|10 // 215798 /// ENSM Gpr126 0.000284826 3.87278NM_008354 // Il12rb2 // interleukin 12 receptor, beta 2 // 6 C1|6 30.81 cM // 16162 /// Il12rb2 0.000164682 3.86428NM_133815 // Lbr // lamin B receptor // 1 H5|1 84.89 cM // 98386 /// ENSMUST00000005003 Lbr 6.98E-08 3.85951NM_011943 // Map2k6 // mitogen-activated protein kinase kinase 6 // 11|11 E1 // 26399 / Map2k6 7.20E-05 3.84675--- 0.000760334 3.84646NM_019455 // Hpgds // hematopoietic prostaglandin D synthase // 6|6 D-E // 54486 /// EN Hpgds 3.00E-07 3.83681ENSMUST00000082387 // mt-Tf // mitochondrially encoded tRNA phenylalanine // --- // --- mt-Tf 0.00108203 3.83094NM_001170537 // Mef2c // myocyte enhancer factor 2C // 13 C3|13 43.68 cM // 17260 /// N Mef2c 1.74E-08 3.82883NM_009791 // Aspm // asp (abnormal spindle)-like, microcephaly associated (Drosophila) Aspm 0.000132014 3.82674--- 0.000282359 3.82285ENSMUST00000181443 // Gm26778 // predicted gene, 26778 // --- // --- Gm26778 2.55E-05 3.81126NM_207161 // Dnph1 // 2-deoxynucleoside 5-phosphate N-hydrolase 1 // 17 C|17 // 381101 Dnph1 0.000426527 3.80679ENSMUST00000082508 // Gm26225 // predicted gene, 26225 // --- // --- Gm26225 0.000428496 3.80384NM_175429 // Kctd12b // potassium channel tetramerisation domain containing 12b // X F3 Kctd12b 1.30E-06 3.79919--- 0.00365792 3.79904--- 0.00194338 3.78955NM_001205336 // Arap3 // ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 3 // 1 Arap3 0.000105374 3.78905--- 0.00489795 3.78207NM_175930 // Rapgef5 // Rap guanine nucleotide exchange factor (GEF) 5 // 12 F2|12 // 2 Rapgef5 5.38E-08 3.77087NM_011920 // Abcg2 // ATP-binding cassette, sub-family G (WHITE), member 2 // 6 B3|6 27 Abcg2 2.06E-06 3.77027NM_010118 // Egr2 // early growth response 2 // 10 B5|10 34.96 cM // 13654 /// XM_00651 Egr2 3.01E-05 3.76818NM_019861 // Ctsf // cathepsin F // 19 A|19 // 56464 /// ENSMUST00000119694 // Ctsf // Ctsf 1.82E-06 3.75315NM_001164763 // Rarres1 // retinoic acid receptor responder (tazarotene induced) 1 // 3 Rarres1 4.83E-05 3.75176NM_175116 // Lpar6 // lysophosphatidic acid receptor 6 // 14 D3|14 // 67168 /// ENSMUST Lpar6 6.62E-08 3.71997NM_178912 // Fancm // Fanconi anemia, complementation group M // 12 C1|12 27.21 cM // 1 Fancm 0.00107912 3.71019NM_001174170 // Serpinb2 // serine (or cysteine) peptidase inhibitor, clade B, member 2 Serpinb2 3.91E-09 3.69084NM_145137 // Mgl2 // macrophage galactose N-acetyl-galactosamine specific lectin 2 // 1 Mgl2 0.00178192 3.68625--- 0.00437657 3.68518--- 0.000729418 3.68518XM_006527625 // Gpr34 // G protein-coupled receptor 34 // X|X A1.3 // 23890 /// ENSMUST Gpr34 0.00013596 3.67062--- 3.79E-06 3.65482NR_002864 // Peg13 // paternally expressed 13 // 15 D3|15 // 353342 Peg13 9.71E-07 3.65028--- 4.54E-05 3.61864NM_019992 // Stap1 // signal transducing adaptor family member 1 // 5 E1|5 // 56792 /// Stap1 9.52E-07 3.61259NM_007681 // Cenpa // centromere protein A // 5 B1|5 16.76 cM // 12615 /// XM_006503708 Cenpa 2.89E-06 3.61232--- 0.00145287 3.61005NM_001101656 // Gm11710 // predicted gene 11710 // 11 E2|11 // 100043123 /// NM_0011016 Gm11710 2.09E-08 3.59523NR_015537 // 9230114K14Rik // RIKEN cDNA 9230114K14 gene // 5 C1|5 // 414108 /// ENSMUS 9230114K14Rik 0.000614704 3.58973ENSMUST00000082406 // mt-Tk // mitochondrially encoded tRNA lysine // --- // --- mt-Tk 0.00129923 3.58863NM_009848 // Entpd1 // ectonucleoside triphosphate diphosphohydrolase 1 // 19 C3|19 34. Entpd1 1.25E-07 3.58389ENSMUST00000174884 // Gm20475 // predicted gene 20475 // --- // --- Gm20475 0.000257835 3.5611NM_010145 // Ephx1 // epoxide hydrolase 1, microsomal // 1 H4|1 84.48 cM // 13849 /// E Ephx1 3.65E-06 3.5596ENSMUST00000092459 // Cd300lh // CD300 antigen like family member H // 11 E2|11 // 3825 Cd300lh 0.000210688 3.54683NM_001166406 // Kif20a // kinesin family member 20A // 18 B1|18 18.69 cM // 19348 /// N Kif20a 1.78E-06 3.52846NR_036450 // Gm14403 // predicted gene 14403 // 2 H4|2 // 433520 Gm14403 0.000126853 3.50974--- 0.00302063 3.49968NM_001111052 // Dclk1 // doublecortin-like kinase 1 // 3|3 D // 13175 /// NM_001111053 Dclk1 1.19E-06 3.49955NM_009690 // Cd5l // CD5 antigen-like // 3 F1|3 // 11801 /// ENSMUST00000015998 // Cd5l Cd5l 1.65E-07 3.4991NM_008079 // Galc // galactosylceramidase // 12 E|12 49.83 cM // 14420 /// ENSMUST00000 Galc 5.19E-06 3.49331NM_145512 // Sft2d2 // SFT2 domain containing 2 // 1 H2.3|1 // 108735 /// ENSMUST000000 Sft2d2 1.47E-07 3.49013NM_133198 // Pygl // liver glycogen phosphorylase // 12 C2|12 29.01 cM // 110095 /// EN Pygl 3.25E-06 3.4713NM_008425 // Kcnj2 // potassium inwardly-rectifying channel, subfamily J, member 2 // 1 Kcnj2 0.000180537 3.45992NM_007988 // Fasn // fatty acid synthase // 11 E2|11 84.56 cM // 14104 /// ENSMUST00000 Fasn 2.65E-08 3.45628NM_001289895 // Tns1 // tensin 1 // 1 C3|1 38.17 cM // 21961 /// NM_027884 // Tns1 // t Tns1 2.13E-07 3.45471NM_001146287 // Cables1 // CDK5 and Abl enzyme substrate 1 // 18|18 A2 // 63955 /// NM_ Cables1 0.000977468 3.45047NM_001161763 // Fmo5 // flavin containing monooxygenase 5 // 3 F2.2|3 // 14263 /// NM_0 Fmo5 1.40E-05 3.44449NM_175164 // Arhgap26 // Rho GTPase activating protein 26 // 18 B3|18 // 71302 /// XM_0 Arhgap26 4.65E-06 3.43509NM_152801 // Arhgef6 // Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6 // X A5|X Arhgef6 4.31E-06 3.42958--- 0.00247493 3.42759NM_144942 // Csad // cysteine sulfinic acid decarboxylase // 15 F3|15 // 246277 /// XM_ Csad 4.17E-06 3.42343

NM_010680 // Lama3 // laminin, alpha 3 // 18 A|18 6.2 cM // 16774 /// ENSMUST0000009207 Lama3 1.25E-06 3.41929NM_001080944 // Atp8b4 // ATPase, class I, type 8B, member 4 // 2 F1|2 // 241633 /// XM Atp8b4 6.84E-07 3.40502NM_001271599 // Sort1 // sortilin 1 // 3 F3|3 // 20661 /// NM_019972 // Sort1 // sortil Sort1 5.94E-09 3.38153NM_023223 // Cdc20 // cell division cycle 20 // 4 D2.1|4 // 107995 /// ENSMUST000000065 Cdc20 7.61E-06 3.38087NM_001195529 // Gm4980 // predicted gene 4980 // 7 E2|7 // 100503386 /// ENSMUST0000017 Gm4980 0.000143364 3.36945ENSMUST00000180988 // Gm26912 // predicted gene, 26912 // --- // --- Gm26912 0.000440622 3.36305NM_001291910 // Adcy9 // adenylate cyclase 9 // 16 B1|16 2.42 cM // 11515 /// NM_009624 Adcy9 9.07E-05 3.35052NM_177606 // Plekhh2 // pleckstrin homology domain containing, family H (with MyTH4 dom Plekhh2 5.14E-05 3.3164--- 2.60E-05 3.31252NM_028372 // Mblac2 // metallo-beta-lactamase domain containing 2 // 13 C3|13 // 72852 Mblac2 9.78E-07 3.31045NM_001123367 // Gm3448 // predicted gene 3448 // 17 A2|17 // 100041639 /// NM_001123368 Gm3448 1.62E-05 3.3031NM_001243762 // Clcn5 // chloride channel 5 // X A1.1|X 3.21 cM // 12728 /// ENSMUST000 Clcn5 2.39E-09 3.30056ENSMUST00000103960 // Gm22935 // predicted gene, 22935 // --- // --- Gm22935 0.00113592 3.29965--- 0.000307924 3.29902--- 0.00185898 3.27594ENSMUST00000163881 // Gm17364 // predicted gene, 17364 // --- // --- Gm17364 0.000129711 3.27038NM_201609 // Zfp652 // zinc finger protein 652 // 11 D|11 // 268469 /// ENSMUST00000091 Zfp652 1.86E-06 3.27008NM_053272 // Dhcr24 // 24-dehydrocholesterol reductase // 4 C7|4 // 74754 /// ENSMUST00 Dhcr24 4.81E-09 3.26981NM_025835 // Pccb // propionyl Coenzyme A carboxylase, beta polypeptide // 9 E4|9 // 66 Pccb 0.000177531 3.26358NM_013464 // Ahr // aryl-hydrocarbon receptor // 12 A3|12 15.78 cM // 11622 /// ENSMUST Ahr 5.07E-05 3.26354--- 0.00138343 3.2613--- 0.000711377 3.2611NM_013599 // Mmp9 // matrix metallopeptidase 9 // 2 H1-H2|2 85.27 cM // 17395 /// ENSMU Mmp9 4.99E-06 3.25363NM_008478 // L1cam // L1 cell adhesion molecule // X A6-B|X 37.43 cM // 16728 /// ENSMU L1cam 0.00095187 3.24735NM_021334 // Itgax // integrin alpha X // 7 F3|7 // 16411 /// ENSMUST00000033053 // Itg Itgax 7.03E-06 3.24195NM_001289915 // Cd83 // CD83 antigen // 13 A4-5|13 21.6 cM // 12522 /// NM_009856 // Cd Cd83 3.65E-06 3.23811NM_011369 // Shcbp1 // Shc SH2-domain binding protein 1 // 8|8 A1.2 // 20419 /// ENSMUS Shcbp1 0.00117839 3.23184NM_001033257 // Phactr2 // phosphatase and actin regulator 2 // 10 A2|10 // 215789 /// Phactr2 4.04E-05 3.21777NM_010330 // Emb // embigin // 13 D2.3|13 // 13723 /// ENSMUST00000022242 // Emb // emb Emb 3.79E-08 3.21594NM_010302 // Gna12 // guanine nucleotide binding protein, alpha 12 // 5 G2|5 79.3 cM // Gna12 5.31E-08 3.21384NM_001146200 // Pik3cg // phosphoinositide-3-kinase, catalytic, gamma polypeptide // 12 Pik3cg 6.47E-08 3.21165NM_024245 // Kif23 // kinesin family member 23 // 9 B|9 // 71819 /// ENSMUST00000034815 Kif23 0.000790652 3.19618NM_175542 // Rttn // rotatin // 18 E4|18 // 246102 /// ENSMUST00000023828 // Rttn // ro Rttn 6.17E-06 3.19607NM_007630 // Ccnb2 // cyclin B2 // 9 D|9 // 12442 /// ENSMUST00000034742 // Ccnb2 // cy Ccnb2 2.29E-05 3.19456NM_008509 // Lpl // lipoprotein lipase // 8 B3.3|8 33.88 cM // 16956 /// ENSMUST0000001 Lpl 1.84E-07 3.1926NM_001081426 // Dip2c // DIP2 disco-interacting protein 2 homolog C (Drosophila) // 13 Dip2c 4.19E-06 3.18692--- 0.000599403 3.18687NM_022881 // Rgs18 // regulator of G-protein signaling 18 // 1 F|1 62.99 cM // 64214 // Rgs18 4.31E-05 3.17918NM_172597 // Txndc16 // thioredoxin domain containing 16 // 14|14 C1 // 70561 /// XM_00 Txndc16 1.70E-06 3.15536ENSMUST00000086363 // Tmem150b // transmembrane protein 150B // 7 A1|7 // 330460 /// NM Tmem150b 3.59E-05 3.14939NM_133738 // Antxr2 // anthrax toxin receptor 2 // 5 E3|5 // 71914 /// ENSMUST000000312 Antxr2 6.78E-07 3.14475NR_003517 // Pisd-ps1 // phosphatidylserine decarboxylase, pseudogene 1 // 11 A1|11 // Pisd-ps1 0.000269848 3.14111NM_010615 // Kif11 // kinesin family member 11 // 19 C2|19 // 16551 /// ENSMUST00000012 Kif11 7.48E-08 3.12206NM_153820 // Arhgap15 // Rho GTPase activating protein 15 // 2 B|2 // 76117 /// XM_0064 Arhgap15 1.56E-05 3.12072--- 0.0036551 3.11708NR_040616 // A130077B15Rik // RIKEN cDNA A130077B15 gene // 10 D2|10 // 319272 A130077B15Rik 0.000176079 3.11499NM_018797 // Plxnc1 // plexin C1 // 10|10 C3 // 54712 /// XM_006513895 // Plxnc1 // ple Plxnc1 2.63E-07 3.11444NM_001291818 // Rhbdf1 // rhomboid family 1 (Drosophila) // 11 A4|11 18.83 cM // 13650 Rhbdf1 0.000118844 3.1141NM_001243049 // Atp6v0a1 // ATPase, H+ transporting, lysosomal V0 subunit A1 // 11 D|11 Atp6v0a1 2.28E-06 3.11134NM_001290376 // Camk1d // calcium/calmodulin-dependent protein kinase ID // 2 A1|2 // 2 Camk1d 6.60E-07 3.1083NM_145938 // Rpp40 // ribonuclease P 40 subunit // 13 A3.3|13 // 208366 /// XM_00651663 Rpp40 0.000893567 3.10772NM_011121 // Plk1 // polo-like kinase 1 // 7 F3|7 65.52 cM // 18817 /// ENSMUST00000033 Plk1 6.45E-06 3.10227NM_144546 // Zfp119a // zinc finger protein 119a // 17 D|17 // 104349 /// XM_006523384 Zfp119a 0.00303568 3.10008NM_027526 // Rasgef1a // RasGEF domain family, member 1A // 6 F1|6 // 70727 /// XM_0065 Rasgef1a 0.0003799 3.08939NM_007929 // Emp2 // epithelial membrane protein 2 // 16 A1|16 5.54 cM // 13731 /// ENS Emp2 1.24E-05 3.08197NM_025806 // Plbd1 // phospholipase B domain containing 1 // 6 G1|6 // 66857 /// ENSMUS Plbd1 1.11E-05 3.07407--- 0.00353496 3.06691--- 5.98E-05 3.06192NM_001110233 // Ngfrap1 // nerve growth factor receptor (TNFRSF16) associated protein 1 Ngfrap1 4.73E-06 3.06087NM_011254 // Rbp1 // retinol binding protein 1, cellular // 9 E3.3|9 51.36 cM // 19659 Rbp1 2.23E-05 3.06008ENSMUST00000179846 // Gm25121 // predicted gene, 25121 // --- // --- Gm25121 0.00137242 3.0516NM_177178 // Lmbrd2 // LMBR1 domain containing 2 // 15 A1|15 // 320506 /// XM_006520092 Lmbrd2 1.42E-06 3.04984--- 0.00364311 3.04217NM_001081176 // Polr3g // polymerase (RNA) III (DNA directed) polypeptide G // 13 C3|13 Polr3g 2.49E-07 3.04169NM_019410 // Pfn2 // profilin 2 // 3 D|3 28.15 cM // 18645 /// ENSMUST00000066882 // Pf Pfn2 1.06E-05 3.04053--- 0.00360467 3.03364NM_001177625 // Ect2 // ect2 oncogene // 3|3 B // 13605 /// NM_001177626 // Ect2 // ect Ect2 3.28E-05 3.02803NM_181595 // Ppp1r9a // protein phosphatase 1, regulatory (inhibitor) subunit 9A // 6 A Ppp1r9a 9.22E-08 3.02656NM_011436 // Sorl1 // sortilin-related receptor, LDLR class A repeats-containing // 9 B Sorl1 9.45E-05 3.02385NM_001199105 // Trp53inp1 // transformation related protein 53 inducible nuclear protei Trp53inp1 7.13E-06 3.01239NM_001290989 // Clstn1 // calsyntenin 1 // 4 E1|4 // 65945 /// NM_023051 // Clstn1 // c Clstn1 1.58E-06 3.01233NM_172588 // Serinc5 // serine incorporator 5 // 13 C3|13 // 218442 /// ENSMUST00000049 Serinc5 1.54E-05 3.01111NM_001033606 // Acsl3 // acyl-CoA synthetase long-chain family member 3 // 1 C4|1 40.84 Acsl3 8.48E-05 3.00604--- 9.72E-06 3.0049NM_021310 // Jmy // junction-mediating and regulatory protein // 13 C3|13 // 57748 /// Jmy 1.30E-06 2.99742NM_175136 // Rnf122 // ring finger protein 122 // 8 A3|8 // 68867 /// XM_006509189 // R Rnf122 0.000107469 2.98662NM_008131 // Glul // glutamate-ammonia ligase (glutamine synthetase) // 1 G2|1 // 14645 Glul 1.04E-07 2.98477NM_001102455 // Aplp2 // amyloid beta (A4) precursor-like protein 2 // 9 A2-B|9 16.66 c Aplp2 4.33E-08 2.97778NM_177089 // Tacc1 // transforming, acidic coiled-coil containing protein 1 // 8 A2|8 / Tacc1 3.86E-06 2.96968NM_001113209 // Nfib // nuclear factor I/B // 4 C4-C6|4 38.4 cM // 18028 /// NM_0011132 Nfib 3.25E-06 2.96767NM_013835 // Trove2 // TROVE domain family, member 2 // 1 F|1 62.54 cM // 20822 /// ENS Trove2 2.14E-06 2.96319NM_027629 // Pgm2l1 // phosphoglucomutase 2-like 1 // 7|7 F1 // 70974 /// XM_006508205 Pgm2l1 5.11E-07 2.96185NM_023326 // Bmyc // brain expressed myelocytomatosis oncogene // 2 A3|2 // 107771 /// Bmyc 0.000197233 2.95565NM_183116 // Slc18b1 // solute carrier family 18, subfamily B, member 1 // 10 A3-A4|10 Slc18b1 0.000877159 2.95467NM_001043335 // Eml1 // echinoderm microtubule associated protein like 1 // 12 F1|12 59 Eml1 9.34E-05 2.95437NM_001164207 // Tmem176b // transmembrane protein 176B // 6 B2.3|6 23.75 cM // 65963 // Tmem176b 5.41E-06 2.95403NM_177646 // Dgkd // diacylglycerol kinase, delta // 1 D|1 // 227333 /// XM_006529471 / Dgkd 5.06E-07 2.95318NM_011712 // Wbp5 // WW domain binding protein 5 // X F1|X // 22381 /// ENSMUST00000048 Wbp5 0.000232029 2.95111NM_001287530 // Arhgap6 // Rho GTPase activating protein 6 // X F5|X // 11856 /// NM_00 Arhgap6 3.53E-08 2.93867NM_026662 // Prps2 // phosphoribosyl pyrophosphate synthetase 2 // X F2-F3|X 78.32 cM / Prps2 1.40E-06 2.93795XM_006525694 // Stard4 // StAR-related lipid transfer (START) domain containing 4 // 18 Stard4 0.000215375 2.93055NM_013743 // Pdk4 // pyruvate dehydrogenase kinase, isoenzyme 4 // 6 A1|6 2.06 cM // 27 Pdk4 3.10E-06 2.92862NM_001112725 // Aldh3a1 // aldehyde dehydrogenase family 3, subfamily A1 // 11 B2|11 37 Aldh3a1 5.96E-05 2.92427NM_146251 // Pnpla7 // patatin-like phospholipase domain containing 7 // 2 A3|2 // 2412 Pnpla7 2.24E-06 2.91871NM_146073 // Zdhhc14 // zinc finger, DHHC domain containing 14 // 17 A1|17 // 224454 // Zdhhc14 4.53E-06 2.91418

NM_009911 // Cxcr4 // chemokine (C-X-C motif) receptor 4 // 1 E4|1 56.43 cM // 12767 // Cxcr4 3.43E-06 2.90916NM_029436 // Klhl24 // kelch-like 24 // 16|16 B1 // 75785 /// ENSMUST00000023509 // Klh Klhl24 5.96E-05 2.90037NM_177231 // Arrb1 // arrestin, beta 1 // 7 E2|7 54.09 cM // 109689 /// NM_178220 // Ar Arrb1 1.25E-08 2.89954NM_001042699 // Syne3 // spectrin repeat containing, nuclear envelope family member 3 / Syne3 0.00010986 2.89934NM_145962 // Pank3 // pantothenate kinase 3 // 11 A4|11 // 211347 /// ENSMUST0000001899 Pank3 1.30E-05 2.89544ENSMUST00000082479 // Gm22245 // predicted gene, 22245 // --- // --- Gm22245 7.40E-05 2.88205ENSMUST00000069568 // Gm9982 // predicted gene 9982 // --- // 791357 /// AK078283 // Gm Gm9982 0.000390598 2.87828NR_029728 // Mirlet7c-1 // microRNA let7c-1 // 16|16 // 387246 /// ENSMUST00000083623 / Mirlet7c-1 0.00149921 2.87664NM_001039511 // Ivns1abp // influenza virus NS1A binding protein // 1 G2|1 // 117198 // Ivns1abp 1.38E-06 2.86757NM_080462 // Hnmt // histamine N-methyltransferase // 2 A3|2 // 140483 /// XM_006497671 Hnmt 1.38E-05 2.86606NM_001033350 // Bank1 // B cell scaffold protein with ankyrin repeats 1 // 3 G3|3 63.04 Bank1 7.46E-05 2.85436NM_177184 // Vps13c // vacuolar protein sorting 13C (yeast) // 9 C|9 // 320528 /// ENSM Vps13c 1.11E-06 2.85277XR_398829 // LOC102641333 // uncharacterized LOC102641333 // --- // 102641333 /// ENSMU LOC102641333 0.000292499 2.85246NM_001286544 // Ccpg1 // cell cycle progression 1 // 9 D|9 40.08 cM // 72278 /// ENSMUS Ccpg1 1.66E-05 2.85227--- 2.91E-05 2.84706NM_027547 // Prdm5 // PR domain containing 5 // 6 C1|6 // 70779 /// XR_377491 // Prdm5 Prdm5 0.000842388 2.84448NM_001042613 // Sepp1 // selenoprotein P, plasma, 1 // 15 A1|15 1.84 cM // 20363 /// NM Sepp1 1.89E-06 2.84028NM_001289877 // Per3 // period circadian clock 3 // 4 E2|4 // 18628 /// NM_001289878 // Per3 1.94E-05 2.83324ENSMUST00000083348 // Gm24455 // predicted gene, 24455 // --- // --- /// AK161656 // Ta Gm24455 0.00108394 2.8304NR_045822 // Gm4890 // predicted gene 4890 // 8 C2|8 // 234479 /// NR_045823 // Gm4890 Gm4890 0.00407254 2.82855NM_177632 // Fam43a // family with sequence similarity 43, member A // 16 B2|16 // 2240 Fam43a 0.000648594 2.82478NM_027934 // Rnf180 // ring finger protein 180 // 13|13 D1 // 71816 /// ENSMUST00000069 Rnf180 2.15E-06 2.81835NM_009441 // Ttc3 // tetratricopeptide repeat domain 3 // 16 C3.3-4|16 55.18 cM // 2212 Ttc3 3.19E-06 2.81638NM_001291190 // Ssh2 // slingshot homolog 2 (Drosophila) // 11 B5|11 // 237860 /// NM_1 Ssh2 4.46E-07 2.80935NM_011712 // Wbp5 // WW domain binding protein 5 // X F1|X // 22381 /// ENSMUST00000048 Wbp5 4.21E-05 2.80829ENSMUST00000106578 // Gm11709 // predicted gene 11709 // --- // --- Gm11709 0.00208524 2.80392ENSMUST00000170967 // Rb1 // retinoblastoma 1 // 14 D3|14 38.73 cM // 19645 Rb1 0.000816021 2.80168NM_001159394 // Nfkbiz // nuclear factor of kappa light polypeptide gene enhancer in B Nfkbiz 0.00480977 2.79892NM_181585 // Pik3r3 // phosphatidylinositol 3 kinase, regulatory subunit, polypeptide 3 Pik3r3 0.00076148 2.7983NM_001081189 // Uprt // uracil phosphoribosyltransferase (FUR1) homolog (S. cerevisiae) Uprt 9.05E-07 2.78981NM_001164275 // Prrg1 // proline rich Gla (G-carboxyglutamic acid) 1 // X B|X // 546336 Prrg1 0.00100796 2.7895NM_009370 // Tgfbr1 // transforming growth factor, beta receptor I // 4 B1|4 26.02 cM / Tgfbr1 1.04E-06 2.78632--- 0.000126983 2.78447NM_001128094 // Atp13a3 // ATPase type 13A3 // 16 B2|16 // 224088 /// NM_001128096 // A Atp13a3 4.05E-07 2.77817NM_001288627 // Emp1 // epithelial membrane protein 1 // 6 G1|6 66.25 cM // 13730 /// N Emp1 2.01E-08 2.7757NM_178415 // Bbs9 // Bardet-Biedl syndrome 9 (human) // 9 A3|9 // 319845 /// NM_181316 Bbs9 1.92E-05 2.76412--- 0.00393597 2.76196NM_172595 // Arl15 // ADP-ribosylation factor-like 15 // 13 D2.2|13 // 218639 /// XM_00 Arl15 0.000357624 2.75866--- 0.00256716 2.75699NM_033314 // Slco2a1 // solute carrier organic anion transporter family, member 2a1 // Slco2a1 0.000175845 2.75599NM_001081363 // Cenpf // centromere protein F // 1 H6|1 95.03 cM // 108000 /// XM_00649 Cenpf 3.25E-05 2.75547NM_001008702 // Dab2 // disabled 2, mitogen-responsive phosphoprotein // 15 A|15 2.15 c Dab2 2.14E-07 2.75435NM_007379 // Abca2 // ATP-binding cassette, sub-family A (ABC1), member 2 // 2 A2-B|2 1 Abca2 1.41E-07 2.7501NR_030609 // Mir511 // microRNA 511 // 2|2 // 100124488 /// ENSMUST00000104704 // Mir51 Mir511 0.000685657 2.74831NM_181415 // Atrnl1 // attractin like 1 // 19 D2|19 // 226255 /// ENSMUST00000077282 // Atrnl1 0.000282647 2.74788NM_022331 // Herpud1 // homocysteine-inducible, endoplasmic reticulum stress-inducible, Herpud1 1.47E-07 2.7463NM_001099738 // Dnajc28 // DnaJ (Hsp40) homolog, subfamily C, member 28 // 16 C3.3|16 / Dnajc28 0.0016587 2.74025NM_028810 // Rnd3 // Rho family GTPase 3 // 2 C1.1|2 // 74194 /// ENSMUST00000017288 // Rnd3 3.60E-05 2.73503NM_178646 // Tigd5 // tigger transposable element derived 5 // 15 D3|15 // 105734 /// E Tigd5 0.000739989 2.73284NM_008710 // Nnt // nicotinamide nucleotide transhydrogenase // 13 D2|13 67.21 cM // 18 Nnt 4.49E-07 2.73271NR_015543 // 2810055G20Rik // RIKEN cDNA 2810055G20 gene // 16 C3.1|16 // 77994 /// ENS 2810055G20Rik 0.00151707 2.73029NM_001001798 // Atp11c // ATPase, class VI, type 11C // X|X A5 // 320940 /// NM_0010378 Atp11c 1.97E-07 2.7276NM_033602 // Peli2 // pellino 2 // 14 C1|14 24.6 cM // 93834 /// XM_006519740 // Peli2 Peli2 8.27E-05 2.72502--- 0.00241011 2.72451NM_019670 // Diap3 // diaphanous homolog 3 (Drosophila) // 14|14 D3 // 56419 /// XM_006 Diap3 0.000138173 2.72246--- 0.00113705 2.72121NM_011055 // Pde3b // phosphodiesterase 3B, cGMP-inhibited // 7 F1|7 59.46 cM // 18576 Pde3b 0.000103277 2.72012NM_019730 // Nme3 // NME/NM23 nucleoside diphosphate kinase 3 // 17 A3.3|17 // 79059 // Nme3 7.44E-05 2.72007NM_175247 // Zfp28 // zinc finger protein 28 // 7 A1|7 // 22690 /// XM_006539742 // Zfp Zfp28 0.000163624 2.71721NM_001040072 // Nynrin // NYN domain and retroviral integrase containing // 14 C3|14 // Nynrin 0.00201582 2.71532NM_001170855 // Trim36 // tripartite motif-containing 36 // 18 C|18 24.41 cM // 28105 / Trim36 0.00131369 2.71382NM_029631 // Abhd14b // abhydrolase domain containing 14b // 9 F1|9 // 76491 /// XM_006 Abhd14b 0.000185814 2.71145AK050884 // D030029J20Rik // RIKEN cDNA D030029J20 gene // 2|2 // 100502854 D030029J20Rik 0.000103037 2.71126NM_016974 // Dbp // D site albumin promoter binding protein // 7 B4|7 29.45 cM // 13170 Dbp 0.000200329 2.70708NM_001001806 // Zfp36l2 // zinc finger protein 36, C3H type-like 2 // 17 E4|17 // 12193 Zfp36l2 4.78E-07 2.70448NM_198105 // Fam120c // family with sequence similarity 120, member C // X|X F2 // 2073 Fam120c 1.84E-05 2.70328NM_010121 // Eif2ak3 // eukaryotic translation initiation factor 2 alpha kinase 3 // 6 Eif2ak3 2.33E-05 2.69706NM_001034891 // Ermard // ER membrane associated RNA degradation // 17 A2|17 // 381062 Ermard 3.23E-06 2.69695NM_001102471 // Cnnm2 // cyclin M2 // 19 C3|19 38.97 cM // 94219 /// NM_033569 // Cnnm2 Cnnm2 0.000383708 2.6945NM_001253708 // Mbnl1 // muscleblind-like 1 (Drosophila) // 3 E1|3 // 56758 /// NM_0012 Mbnl1 5.84E-08 2.69341NM_026674 // Aph1c // anterior pharynx defective 1c homolog (C. elegans) // 9 C|9 // 68 Aph1c 4.44E-06 2.69296NM_133721 // Itga9 // integrin alpha 9 // 9 F3|9 70.32 cM // 104099 /// ENSMUST00000044 Itga9 7.92E-05 2.68998--- 0.000495118 2.68974NM_173442 // Gcnt1 // glucosaminyl (N-acetyl) transferase 1, core 2 // 19 B|19 12.75 cM Gcnt1 4.71E-05 2.68947NM_177151 // Vps13b // vacuolar protein sorting 13B (yeast) // 15 B3.1|15 // 666173 /// Vps13b 6.22E-08 2.68877XM_006541085 // 2410002F23Rik // RIKEN cDNA 2410002F23 gene // 7 B4|7 // 668661 /// ENS 2410002F23Rik 6.63E-07 2.68743NM_010764 // Man2b1 // mannosidase 2, alpha B1 // 8 C2|8 41.55 cM // 17159 /// XM_00653 Man2b1 3.00E-07 2.68723NM_007447 // Ang // angiogenin, ribonuclease, RNase A family, 5 // 14 B-C1|14 26.37 cM Ang 0.000288553 2.6865NM_172573 // Engase // endo-beta-N-acetylglucosaminidase // 11 E2|11 // 217364 /// ENSM Engase 0.000259757 2.68546NM_145853 // Tpcn1 // two pore channel 1 // 5 F|5 // 252972 /// ENSMUST00000046426 // T Tpcn1 0.00396998 2.6749ENSMUST00000150912 // Stard9 // START domain containing 9 // 2 E5|2 // 668880 /// ENSMU Stard9 1.36E-05 2.67437NM_013470 // Anxa3 // annexin A3 // 5 E3|5 47.29 cM // 11745 /// ENSMUST00000031447 // Anxa3 1.44E-07 2.66771NM_026058 // Cers4 // ceramide synthase 4 // 8|8 A1.2 // 67260 /// XM_006508863 // Cers Cers4 1.18E-05 2.66645--- 0.00103193 2.66558NM_027973 // Cenpu // centromere protein U // 8|8 B2 // 71876 /// ENSMUST00000034045 // Cenpu 0.000938815 2.6655NM_007836 // Gadd45a // growth arrest and DNA-damage-inducible 45 alpha // 6 C1|6 // 13 Gadd45a 4.46E-07 2.66146NM_001038604 // Clec5a // C-type lectin domain family 5, member a // 6|6 B2 // 23845 // Clec5a 1.70E-05 2.66051AK020421 // Hist1h3d // histone cluster 1, H3d // 13 A2-A3|13 // 319149 Hist1h3d 0.00140555 2.65649NM_010357 // Gsta4 // glutathione S-transferase, alpha 4 // 9 E1|9 // 14860 /// ENSMUST Gsta4 5.15E-05 2.65518--- 0.00165309 2.65374NM_020581 // Angptl4 // angiopoietin-like 4 // 17 B1|17 // 57875 /// ENSMUST00000002360 Angptl4 1.52E-06 2.65372NM_175158 // Utp20 // UTP20, small subunit (SSU) processome component, homolog (yeast) Utp20 2.51E-06 2.65236NM_013881 // Ulk2 // unc-51 like kinase 2 // 11 B2|11 // 29869 /// XM_006533508 // Ulk2 Ulk2 7.50E-06 2.64127NM_001253822 // Irx3 // Iroquois related homeobox 3 // 8 C5|8 44.55 cM // 16373 /// NM_ Irx3 0.000882374 2.64076NM_001163336 // Atp2a3 // ATPase, Ca++ transporting, ubiquitous // 11 B4|11 // 53313 // Atp2a3 0.00369041 2.63739

NM_001190320 // Clec4n // C-type lectin domain family 4, member n // 6 F3|6 58.3 cM // Clec4n 9.64E-07 2.63653NM_009592 // Abcb7 // ATP-binding cassette, sub-family B (MDR/TAP), member 7 // X C-D|X Abcb7 1.95E-06 2.63174ENSMUST00000140646 // Gm15513 // predicted gene 15513 // --- // --- Gm15513 0.00239284 2.62594NM_008514 // Lrp6 // low density lipoprotein receptor-related protein 6 // 6 G1|6 65.37 Lrp6 1.18E-07 2.62453NM_001123367 // Gm3448 // predicted gene 3448 // 17 A2|17 // 100041639 /// NM_001123368 Gm3448 7.64E-05 2.62376NM_027495 // Tmem144 // transmembrane protein 144 // 3|3 F1 // 70652 /// XM_006502057 / Tmem144 0.000220331 2.61758NM_008628 // Msh2 // mutS homolog 2 (E. coli) // 17 E4|17 57.87 cM // 17685 /// ENSMUST Msh2 0.000610496 2.61742NM_009533 // Xrcc5 // X-ray repair complementing defective repair in Chinese hamster ce Xrcc5 0.000890568 2.61738NM_007679 // Cebpd // CCAAT/enhancer binding protein (C/EBP), delta // 16 A2|16 10.09 c Cebpd 0.00100017 2.61385NM_001081128 // Mtr // 5-methyltetrahydrofolate-homocysteine methyltransferase // 13 A1 Mtr 0.00030823 2.61353NM_015737 // Galnt4 // UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosa Galnt4 0.000232515 2.60389NM_025840 // Bzw2 // basic leucine zipper and W2 domains 2 // 12|12 B2 // 66912 /// XM_ Bzw2 0.000172654 2.59772NM_001174155 // Rasgrp4 // RAS guanyl releasing protein 4 // 7 B1|7 16.94 cM // 233046 Rasgrp4 0.000797379 2.59563NM_175331 // Nt5dc3 // 5-nucleotidase domain containing 3 // 10 C1|10 // 103466 /// ENS Nt5dc3 7.61E-06 2.5952XM_006508139 // Rgs10 // regulator of G-protein signalling 10 // 7 F3|7 // 67865 /// NM Rgs10 0.000100556 2.59345NM_001037987 // Edil3 // EGF-like repeats and discoidin I-like domains 3 // 13 C3|13 // Edil3 0.000515843 2.59125NM_001146010 // Fchsd2 // FCH and double SH3 domains 2 // 7 E3|7 // 207278 /// NM_19901 Fchsd2 7.04E-07 2.58852NM_177586 // Eif5a2 // eukaryotic translation initiation factor 5A2 // 3 A3|3 // 208691 Eif5a2 1.89E-06 2.58564NM_009657 // Aldoc // aldolase C, fructose-bisphosphate // 11 B5|11 46.74 cM // 11676 / Aldoc 4.47E-05 2.58403NM_026785 // Ube2c // ubiquitin-conjugating enzyme E2C // 2 H3|2 85.27 cM // 68612 /// Ube2c 0.000320567 2.58333NM_028370 // Pot1b // protection of telomeres 1B // 17 C|17 // 72836 /// XM_006544959 / Pot1b 0.000451917 2.58115--- 0.000207327 2.57881--- 0.000207327 2.57881NM_139232 // Fgd4 // FYVE, RhoGEF and PH domain containing 4 // 16 A3|16 // 224014 /// Fgd4 1.09E-05 2.57735NM_172260 // Cep68 // centrosomal protein 68 // 11 A3.1|11 12.92 cM // 216543 /// XM_00 Cep68 0.000100636 2.57365NM_138672 // Stab1 // stabilin 1 // 14 B|14 // 192187 /// ENSMUST00000036618 // Stab1 / Stab1 5.58E-08 2.57318NM_207237 // Man1c1 // mannosidase, alpha, class 1C, member 1 // 4 D3|4 // 230815 /// X Man1c1 2.30E-06 2.57265NM_001285831 // Far1 // fatty acyl CoA reductase 1 // 7|7 F2 // 67420 /// NM_027379 // Far1 6.74E-06 2.57231--- 0.000874605 2.56871NM_008115 // Gfra2 // glial cell line derived neurotrophic factor family receptor alpha Gfra2 2.74E-05 2.56861XM_006496909 // BC055324 // cDNA sequence BC055324 // 1 H2.2|1 // 381306 /// XM_0064969 BC055324 0.00411569 2.5686NM_001033420 // Dock1 // dedicator of cytokinesis 1 // 7 F3|7 // 330662 /// ENSMUST0000 Dock1 4.22E-05 2.56588NM_010188 // Fcgr3 // Fc receptor, IgG, low affinity III // 1 H3|1 78.8 cM // 14131 /// Fcgr3 1.32E-05 2.56239NM_183390 // Klhl6 // kelch-like 6 // 16 A3|16 // 239743 /// ENSMUST00000058839 // Klhl Klhl6 7.31E-05 2.56061NM_134054 // Sptssa // serine palmitoyltransferase, small subunit A // 12 C1|12 // 1047 Sptssa 0.000450197 2.56003NM_001135149 // Slc39a8 // solute carrier family 39 (metal ion transporter), member 8 / Slc39a8 3.87E-05 2.55978NM_170758 // Cd300a // CD300A antigen // 11 E2|11 80.54 cM // 217303 /// XM_006533069 / Cd300a 8.98E-06 2.55721ENSMUST00000075558 // Hist2h3b // histone cluster 2, H3b // 3 F2.1|3 // 319154 /// ENSM Hist2h3b 0.00385528 2.55715NM_145466 // Ggact // gamma-glutamylamine cyclotransferase // 14 E5|14 // 223267 /// XM Ggact 0.000280921 2.55626NM_145443 // L2hgdh // L-2-hydroxyglutarate dehydrogenase // 12 C2|12 // 217666 /// ENS L2hgdh 0.0039648 2.55431NM_001110780 // Syn1 // synapsin I // X A1-A4|X 16.37 cM // 20964 /// NM_013680 // Syn1 Syn1 6.73E-05 2.55369ENSMUST00000101077 // A530017D24Rik // RIKEN cDNA A530017D24 gene // --- // --- /// ENS A530017D24Rik 3.81E-05 2.5535NM_001085383 // Anxa9 // annexin A9 // 3|3 F2 // 71790 /// NM_023628 // Anxa9 // annexi Anxa9 6.57E-05 2.55124NM_133898 // N4bp2l1 // NEDD4 binding protein 2-like 1 // 5 G3|5 // 100637 /// ENSMUST0 N4bp2l1 4.77E-05 2.54656NM_019656 // Tspan6 // tetraspanin 6 // X E3|X // 56496 /// ENSMUST00000087557 // Tspan Tspan6 0.000506803 2.54645ENSMUST00000082387 // mt-Tf // mitochondrially encoded tRNA phenylalanine // --- // --- mt-Tf 0.00535983 2.54641NM_207301 // Wrb // tryptophan rich basic protein // 16 C4|16 // 71446 /// XM_006523091 Wrb 9.11E-05 2.54398NM_001045513 // Raph1 // Ras association (RalGDS/AF-6) and pleckstrin homology domains Raph1 0.00016159 2.54167NM_010497 // Idh1 // isocitrate dehydrogenase 1 (NADP+), soluble // 1 C2|1 32.91 cM // Idh1 2.32E-07 2.54011NM_001134829 // Lpgat1 // lysophosphatidylglycerol acyltransferase 1 // 1 H6|1 // 22685 Lpgat1 7.85E-06 2.53881NM_009061 // Rgs2 // regulator of G-protein signaling 2 // 1 F|1 62.56 cM // 19735 /// Rgs2 1.27E-07 2.53859--- 0.000820083 2.53683NM_145599 // Tmem184c // transmembrane protein 184C // 8 C1|8 // 234463 /// XM_00653085 Tmem184c 8.17E-07 2.53421--- 8.23E-05 2.53397--- 8.23E-05 2.53397--- 0.00516648 2.53213NM_001135577 // Smim13 // small integral membrane protein 13 // 13A4|13 // 108934 /// E Smim13 0.000340115 2.52993NM_146136 // Slc16a4 // solute carrier family 16 (monocarboxylic acid transporters), me Slc16a4 0.00103224 2.52952--- 7.60E-05 2.52874NM_011937 // Gnpda1 // glucosamine-6-phosphate deaminase 1 // 18 B3|18 // 26384 /// ENS Gnpda1 5.49E-06 2.52581NM_001081433 // Ankrd44 // ankyrin repeat domain 44 // 1 C1.1|1 // 329154 /// ENSMUST00 Ankrd44 1.44E-06 2.52514--- 0.00253136 2.52389NM_146234 // Mmgt1 // membrane magnesium transporter 1 // X A5|X // 236792 /// ENSMUST0 Mmgt1 2.44E-05 2.52198NM_199033 // Tsen2 // tRNA splicing endonuclease 2 homolog (S. cerevisiae) // 6 E3|6 // Tsen2 0.00364448 2.51822NM_199221 // Cd300lb // CD300 antigen like family member B // 11 E2|11 // 217304 /// EN Cd300lb 4.29E-07 2.5154NM_145519 // Farp2 // FERM, RhoGEF and pleckstrin domain protein 2 // 1 D|1 // 227377 / Farp2 0.000227654 2.51285NM_025314 // Dtd1 // D-tyrosyl-tRNA deacylase 1 // 2|2 H1 // 66044 /// ENSMUST000000289 Dtd1 3.34E-06 2.5126NM_175507 // Slc35g1 // solute carrier family 35, member G1 // 19 C3|19 // 240660 /// E Slc35g1 6.56E-05 2.50934NM_008706 // Nqo1 // NAD(P)H dehydrogenase, quinone 1 // 8 D3|8 54.08 cM // 18104 /// E Nqo1 6.11E-07 2.5078--- 0.00149701 2.50412NM_008855 // Prkcb // protein kinase C, beta // 7 F3|7 65.75 cM // 18751 /// ENSMUST000 Prkcb 7.25E-07 2.50325NM_026482 // Atp2b1 // ATPase, Ca++ transporting, plasma membrane 1 // 10|10 C3 // 6797 Atp2b1 5.51E-06 2.50278NM_026178 // Mmd // monocyte to macrophage differentiation-associated // 11 C|11 // 674 Mmd 6.44E-06 2.50069NM_030098 // Rnase6 // ribonuclease, RNase A family, 6 // 14 C1|14 // 78416 /// ENSMUST Rnase6 3.07E-05 2.49901NM_010511 // Ifngr1 // interferon gamma receptor 1 // 10 A3|10 8.49 cM // 15979 /// ENS Ifngr1 3.13E-05 2.49792NM_019654 // Socs5 // suppressor of cytokine signaling 5 // 17 E4|17 // 56468 /// XM_00 Socs5 0.000432248 2.49713NM_001290805 // Kif3a // kinesin family member 3A // 11 A5-B1|11 31.97 cM // 16568 /// Kif3a 5.89E-07 2.49303NM_172619 // Adamts10 // a disintegrin-like and metallopeptidase (reprolysin type) with Adamts10 0.0005632 2.48898NM_009828 // Ccna2 // cyclin A2 // 3 B|3 17.67 cM // 12428 /// ENSMUST00000029270 // Cc Ccna2 4.54E-06 2.48756XR_376691 // Adam22 // a disintegrin and metallopeptidase domain 22 // 5 A1|5 3.39 cM / Adam22 0.000579776 2.48279NM_177325 // Tsr1 // TSR1 20S rRNA accumulation // 11 B5|11 // 104662 /// ENSMUST000000 Tsr1 0.000171877 2.48102NM_010633 // Uhmk1 // U2AF homology motif (UHM) kinase 1 // 1|1 H2 // 16589 /// ENSMUST Uhmk1 9.12E-07 2.47988NM_011507 // Suclg2 // succinate-Coenzyme A ligase, GDP-forming, beta subunit // 6 D3|6 Suclg2 1.22E-06 2.47687NM_183046 // Kif20b // kinesin family member 20B // 19 C2|19 // 240641 /// ENSMUST00000 Kif20b 1.44E-05 2.47623AK085917 // 2610209C05Rik // RIKEN cDNA 2610209C05 gene // 6|6 // 70449 /// AK016706 // 2610209C05Rik 0.000120288 2.47515NM_001115130 // Zbtb44 // zinc finger and BTB domain containing 44 // 9 A4|9 // 235132 Zbtb44 6.14E-06 2.46528NM_024223 // Crip2 // cysteine rich protein 2 // 12 F1|12 61.57 cM // 68337 /// XM_0065 Crip2 0.000129804 2.46455NM_001037955 // Dusp22 // dual specificity phosphatase 22 // 13 A3.2|13 // 105352 /// N Dusp22 3.69E-07 2.46181NM_001110843 // Cacna2d1 // calcium channel, voltage-dependent, alpha2/delta subunit 1 Cacna2d1 8.43E-05 2.46168NM_001160235 // Fam168b // family with sequence similarity 168, member B // 1 B|1 // 21 Fam168b 1.80E-06 2.46052NM_008624 // Mras // muscle and microspikes RAS // 9 E3.3|9 // 17532 /// XM_006510826 / Mras 0.000218478 2.45582NM_001100449 // Taf4b // TAF4B RNA polymerase II, TATA box binding protein (TBP)-associ Taf4b 0.000167241 2.4526--- 0.00375646 2.45209--- 0.000439411 2.44622NM_176996 // Smo // smoothened homolog (Drosophila) // 6 A3.3|6 12.36 cM // 319757 /// Smo 9.73E-05 2.44377

NM_028131 // Cenpn // centromere protein N // 8 E1|8 // 72155 /// ENSMUST00000034205 // Cenpn 0.00034282 2.44332NM_001177572 // Slc25a13 // solute carrier family 25 (mitochondrial carrier, adenine nu Slc25a13 0.00354006 2.43687NM_001081252 // Uggt2 // UDP-glucose glycoprotein glucosyltransferase 2 // 14 E4|14 // Uggt2 5.47E-05 2.43667NM_023284 // Nuf2 // NUF2, NDC80 kinetochore complex component, homolog (S. cerevisiae) Nuf2 0.000311847 2.43625NM_029249 // Parpbp // PARP1 binding protein // 10 C2|10 // 75317 /// ENSMUST0000004851 Parpbp 0.00116439 2.43617NM_028335 // Zfp248 // zinc finger protein 248 // 6 F1|6 // 72720 /// XM_006506676 // Z Zfp248 7.70E-05 2.43335NM_178653 // Sccpdh // saccharopine dehydrogenase (putative) // 1 H4|1 // 109232 /// EN Sccpdh 6.30E-05 2.43324NM_001164362 // Cep55 // centrosomal protein 55 // 19|19 C3 // 74107 /// NM_028293 // C Cep55 0.00133479 2.43059NM_010028 // Ddx3x // DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked // X A1. Ddx3x 0.00056903 2.42982NM_001163713 // Tufm // Tu translation elongation factor, mitochondrial // 7 F3|7 // 23 Tufm 0.00500303 2.42828NM_001282000 // Rbl2 // retinoblastoma-like 2 // 8 C5|8 44.25 cM // 19651 /// NM_001282 Rbl2 5.26E-09 2.42616NM_010137 // Epas1 // endothelial PAS domain protein 1 // 17 E4|17 // 13819 /// ENSMUST Epas1 6.73E-05 2.42334NM_029701 // Spcs3 // signal peptidase complex subunit 3 homolog (S. cerevisiae) // 8 B Spcs3 2.28E-06 2.42303NM_010189 // Fcgrt // Fc receptor, IgG, alpha chain transporter // 7 B4|7 29.12 cM // 1 Fcgrt 1.08E-05 2.4217NR_030499 // Mir505 // microRNA 505 // X|X // 751545 /// ENSMUST00000093573 // Mir505 / Mir505 0.00340978 2.42139NM_178929 // Kazald1 // Kazal-type serine peptidase inhibitor domain 1 // 19 C3|19 // 1 Kazald1 0.00448664 2.42075NM_175403 // Mlec // malectin // 5 F|5 55.99 cM // 109154 /// ENSMUST00000053271 // Mle Mlec 7.00E-08 2.42073NM_001123367 // Gm3448 // predicted gene 3448 // 17 A2|17 // 100041639 /// NM_001123368 Gm3448 0.000159604 2.42061--- 0.00320475 2.41975NM_011334 // Clcn4-2 // chloride channel 4-2 // 7 A1|7 4.23 cM // 12727 /// XM_00653950 Clcn4-2 2.17E-05 2.41928NM_001081680 // Zfp72 // zinc finger protein 72 // 13 C1|13 // 238722 /// ENSMUST000000 Zfp72 0.00517892 2.41865ENSMUST00000169406 // Gm1818 // predicted gene 1818 // 12 B3|12 // 217536 /// M74555 // Gm1818 0.000378154 2.41583NM_008892 // Pola1 // polymerase (DNA directed), alpha 1 // X C-D|X 41.06 cM // 18968 / Pola1 0.000146094 2.41541NM_019487 // Hebp2 // heme binding protein 2 // 10|10 A2 // 56016 /// ENSMUST0000002000 Hebp2 0.00202498 2.41456NM_144860 // Mib1 // mindbomb homolog 1 (Drosophila) // 18 A1|18 // 225164 /// XM_00652 Mib1 3.24E-05 2.41437NM_031191 // Prl2c2 // prolactin family 2, subfamily c, member 2 // 13 A1|13 5.18 cM // Prl2c2 0.00385749 2.41384NM_008568 // Mcm7 // minichromosome maintenance deficient 7 (S. cerevisiae) // 5|5 G1 / Mcm7 6.14E-07 2.41059NM_019864 // Atr // ataxia telangiectasia and Rad3 related // 9 E4|9 // 245000 /// ENSM Atr 0.000249444 2.40929NM_022018 // Fam129a // family with sequence similarity 129, member A // 1 G2|1 // 6391 Fam129a 2.67E-06 2.40873NM_007472 // Aqp1 // aquaporin 1 // 6 B3|6 27.38 cM // 11826 /// ENSMUST00000004774 // Aqp1 0.00538278 2.40764NM_001291211 // Pcmtd2 // protein-L-isoaspartate (D-aspartate) O-methyltransferase doma Pcmtd2 1.42E-05 2.40735--- 0.00232149 2.40711NM_010146 // Epm2a // epilepsy, progressive myoclonic epilepsy, type 2 gene alpha // 10 Epm2a 0.000376338 2.40407NM_001110337 // Gprc5c // G protein-coupled receptor, family C, group 5, member C // 11 Gprc5c 4.49E-05 2.40239NM_001252192 // Eya1 // eyes absent 1 homolog (Drosophila) // 1 A3|1 4.31 cM // 14048 / Eya1 4.82E-06 2.40226NM_212445 // Kdelc2 // KDEL (Lys-Asp-Glu-Leu) containing 2 // 9 A5.3|9 // 68304 /// ENS Kdelc2 4.58E-05 2.40103NM_010831 // Sik1 // salt inducible kinase 1 // 17 B1|17 17.25 cM // 17691 /// ENSMUST0 Sik1 0.00138225 2.39648NM_010576 // Itga4 // integrin alpha 4 // 2 C3|2 47.38 cM // 16401 /// ENSMUST000000999 Itga4 1.36E-05 2.39574NM_010864 // Myo5a // myosin VA // 9 D|9 42.26 cM // 17918 /// ENSMUST00000123128 // My Myo5a 1.01E-07 2.39492NM_001163640 // Chn2 // chimerin 2 // 6 B3|6 // 69993 /// NM_023543 // Chn2 // chimerin Chn2 0.000473274 2.39345--- 0.000716631 2.39181NM_080855 // Zcchc14 // zinc finger, CCHC domain containing 14 // 8 E1|8 // 142682 /// Zcchc14 0.00119 2.39059--- 0.000539799 2.39012--- 0.00305038 2.38896NM_001276452 // Slc17a5 // solute carrier family 17 (anion/sugar transporter), member 5 Slc17a5 5.79E-06 2.38623NM_183308 // Pon2 // paraoxonase 2 // 6 A1|6 1.99 cM // 330260 /// ENSMUST00000057792 / Pon2 2.21E-05 2.38604NM_001081392 // Mdn1 // midasin homolog (yeast) // 4 A5|4 14.3 cM // 100019 /// ENSMUST Mdn1 4.24E-05 2.38587NM_028233 // Lrpprc // leucine-rich PPR-motif containing // 17 E4|17 // 72416 /// ENSMU Lrpprc 5.70E-07 2.38353--- 0.00149548 2.38352NM_010288 // Gja1 // gap junction protein, alpha 1 // 10 B4|10 28.64 cM // 14609 /// EN Gja1 7.03E-06 2.38287NM_144916 // Tmem150a // transmembrane protein 150A // 6 C1|6 // 232086 /// ENSMUST0000 Tmem150a 1.29E-05 2.3821NM_001290993 // Slc30a4 // solute carrier family 30 (zinc transporter), member 4 // 2 E Slc30a4 1.20E-06 2.38091NM_009517 // Zmat3 // zinc finger matrin type 3 // 3|3 B // 22401 /// ENSMUST0000002919 Zmat3 0.000122793 2.38086XR_387077 // Ap1s2 // adaptor-related protein complex 1, sigma 2 subunit // X F5|X // 1 Ap1s2 1.52E-06 2.37968NM_001136073 // Nfatc2 // nuclear factor of activated T cells, cytoplasmic, calcineurin Nfatc2 1.12E-05 2.37811NM_001037859 // Csf1r // colony stimulating factor 1 receptor // 18 D|18 34.41 cM // 12 Csf1r 4.95E-08 2.37746XM_006527412 // Rab3il1 // RAB3A interacting protein (rabin3)-like 1 // 19 A|19 // 7476 Rab3il1 4.42E-06 2.37706NM_025557 // Pcp4l1 // Purkinje cell protein 4-like 1 // 1 H3|1 // 66425 /// XM_0064969 Pcp4l1 0.00100998 2.37476--- 0.00446875 2.37434NM_001289522 // Cad // carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, an Cad 2.95E-05 2.3724NM_001290308 // Col12a1 // collagen, type XII, alpha 1 // 9 E1|9 43.82 cM // 12816 /// Col12a1 0.000172718 2.37177NM_001159369 // Polq // polymerase (DNA directed), theta // 16 B3|16 26.32 cM // 77782 Polq 0.000114734 2.37099NM_030724 // Uck2 // uridine-cytidine kinase 2 // 1 H2.3|1 // 80914 /// XM_006497039 // Uck2 1.52E-05 2.37088NM_172514 // Tmem71 // transmembrane protein 71 // 15 D2|15 // 213068 /// ENSMUST000000 Tmem71 0.000130557 2.3705NM_198308 // Pdpr // pyruvate dehydrogenase phosphatase regulatory subunit // 8 E1|8 // Pdpr 3.95E-05 2.36718NM_008605 // Mmp12 // matrix metallopeptidase 12 // 9 A1|9 2.46 cM // 17381 /// XM_0065 Mmp12 1.00E-07 2.36714NM_008885 // Pmp22 // peripheral myelin protein 22 // 11 B3|11 38.99 cM // 18858 /// EN Pmp22 3.10E-06 2.3656NM_011576 // Tfpi // tissue factor pathway inhibitor // 2 D|2 // 21788 /// XM_006499148 Tfpi 0.00493388 2.3642ENSMUST00000153599 // Gm11940 // predicted gene 11940 // --- // --- Gm11940 0.00239234 2.36399NM_172600 // Tmem260 // transmembrane protein 260 // 14 C1|14 // 218989 /// XM_00651883 Tmem260 7.09E-05 2.36139--- 3.97E-05 2.35764NM_001004140 // Ckap2 // cytoskeleton associated protein 2 // 8 A2|8 // 80986 /// XM_00 Ckap2 2.68E-06 2.35704NM_001271587 // Eps8 // epidermal growth factor receptor pathway substrate 8 // 6 G1|6 Eps8 5.61E-05 2.35652NM_001164099 // Add3 // adducin 3 (gamma) // 19 D2|19 47.18 cM // 27360 /// NM_00116410 Add3 0.000514158 2.35313NM_183195 // Marveld1 // MARVEL (membrane-associating) domain containing 1 // 19 C3|19 Marveld1 0.000221593 2.34922NM_172616 // C330027C09Rik // RIKEN cDNA C330027C09 gene // 16 B5|16 // 224171 /// ENSM C330027C09Rik 0.00018978 2.34826NM_172443 // Tbc1d16 // TBC1 domain family, member 16 // 11 E2|11 // 207592 /// ENSMUST Tbc1d16 0.00026492 2.34629ENSMUST00000113438 // Adamts9 // a disintegrin-like and metallopeptidase (reprolysin ty Adamts9 0.00269444 2.34618NM_001167914 // Atxn3 // ataxin 3 // 12 E|12 // 110616 /// NM_029705 // Atxn3 // ataxin Atxn3 1.41E-05 2.34485NM_178711 // Plscr4 // phospholipid scramblase 4 // 9 E3.3|9 // 235527 /// ENSMUST00000 Plscr4 0.000147885 2.34293NM_013454 // Abca1 // ATP-binding cassette, sub-family A (ABC1), member 1 // 4 A5-B3|4 Abca1 1.32E-09 2.34291--- 0.00329738 2.3414NM_009072 // Rock2 // Rho-associated coiled-coil containing protein kinase 2 // 12|12 A Rock2 3.92E-05 2.33984NM_008823 // Cfp // complement factor properdin // X A3|X 16.44 cM // 18636 /// XR_3868 Cfp 8.33E-06 2.33979NM_001098222 // Bhlhb9 // basic helix-loop-helix domain containing, class B9 // X F1|X Bhlhb9 0.00202418 2.33936NM_011352 // Sema7a // sema domain, immunoglobulin domain (Ig), and GPI membrane anchor Sema7a 3.59E-06 2.33705NM_001098271 // Tmem176a // transmembrane protein 176A // 6 B2.3|6 // 66058 /// NM_0253 Tmem176a 0.00128472 2.33558NM_028493 // Rhobtb3 // Rho-related BTB domain containing 3 // 13 C1|13 // 73296 /// EN Rhobtb3 0.000708657 2.33508NM_052976 // Ophn1 // oligophrenin 1 // X|X C2 // 94190 /// ENSMUST00000033560 // Ophn1 Ophn1 1.93E-06 2.33361NM_010139 // Epha2 // Eph receptor A2 // 4 D-E|4 73.67 cM // 13836 /// ENSMUST000000066 Epha2 0.00123599 2.33247NM_010424 // Hfe // hemochromatosis // 13 A2-A4|13 9.88 cM // 15216 /// XM_006516556 // Hfe 3.96E-05 2.3324--- 0.00123766 2.33187NM_024288 // Rmnd5a // required for meiotic nuclear division 5 homolog A (S. cerevisiae Rmnd5a 5.91E-05 2.3303NM_030263 // Psd3 // pleckstrin and Sec7 domain containing 3 // 8 B3.3|8 // 234353 /// Psd3 0.00108267 2.32752NR_039562 // Mir5103 // microRNA 5103 // 1|1 13.22 cM // 100628580 /// ENSMUST000001751 Mir5103 1.10E-05 2.32648

ENSMUST00000153830 // Fam213a // family with sequence similarity 213, member A // 14 B| Fam213a 1.95E-05 2.32555NM_008292 // Hsd17b4 // hydroxysteroid (17-beta) dehydrogenase 4 // 18 D1|18 // 15488 / Hsd17b4 3.03E-06 2.32295--- 0.000335894 2.32115NM_001163616 // 1810011H11Rik // RIKEN cDNA 1810011H11 gene // 14 B|14 // 69069 /// XR_ 1810011H11Rik 0.00035441 2.31871NM_001113470 // Ctdsp2 // CTD (carboxy-terminal domain, RNA polymerase II, polypeptide Ctdsp2 1.47E-05 2.31511NM_009769 // Klf5 // Kruppel-like factor 5 // 14 E2.2|14 // 12224 /// ENSMUST0000000527 Klf5 0.000590116 2.31084NM_001033167 // Slc22a23 // solute carrier family 22, member 23 // 13 A3.3|13 // 73102 Slc22a23 0.000354847 2.31065NM_001110231 // Celf2 // CUGBP, Elav-like family member 2 // 2|2 A2-A3 // 14007 /// NM_ Celf2 1.28E-05 2.30556ENSMUST00000083266 // Gm24613 // predicted gene, 24613 // --- // --- Gm24613 0.00153974 2.30278NM_008026 // Fli1 // Friend leukemia integration 1 // 9 A4|9 17.74 cM // 14247 /// XM_0 Fli1 1.86E-06 2.30278NM_172134 // Pdxk // pyridoxal (pyridoxine, vitamin B6) kinase // 10 C1|10 39.72 cM // Pdxk 2.09E-05 2.30248NM_001011782 // Olfr543 // olfactory receptor 543 // 7 E3|7 // 257947 /// ENSMUST000000 Olfr543 0.0051367 2.30031NM_008924 // Prkar2a // protein kinase, cAMP dependent regulatory, type II alpha // 9 F Prkar2a 4.05E-06 2.29886NM_026268 // Dusp6 // dual specificity phosphatase 6 // 10|10 C3 // 67603 /// ENSMUST00 Dusp6 2.55E-07 2.29812NM_007763 // Crip1 // cysteine-rich protein 1 (intestinal) // 12 F1|12 61.59 cM // 1292 Crip1 0.000163911 2.29679NM_172617 // Zfp523 // zinc finger protein 523 // 17 A3.3|17 // 224656 /// XR_385316 // Zfp523 2.60E-05 2.29576NM_198605 // Ska3 // spindle and kinetochore associated complex subunit 3 // 14 C3|14 / Ska3 0.000121069 2.29406NM_010421 // Hexa // hexosaminidase A // 9 B|9 32.02 cM // 15211 /// ENSMUST00000026262 Hexa 5.05E-08 2.29395NM_175514 // Fam171b // family with sequence similarity 171, member B // 2 D|2 // 24152 Fam171b 0.00133391 2.29394NM_009104 // Rrm2 // ribonucleotide reductase M2 // 12 A1.3|12 8.5 cM // 20135 /// ENSM Rrm2 8.31E-07 2.29365NM_009730 // Atrn // attractin // 2 F1|2 63.26 cM // 11990 /// ENSMUST00000028781 // At Atrn 2.06E-06 2.29269NM_001014973 // Snx13 // sorting nexin 13 // 12 A3|12 // 217463 /// ENSMUST00000048519 Snx13 1.78E-06 2.29127NM_001081298 // Lphn2 // latrophilin 2 // 3 H3|3 // 99633 /// XM_006502443 // Lphn2 // Lphn2 8.68E-06 2.28923NM_001159538 // Fgd2 // FYVE, RhoGEF and PH domain containing 2 // 17 A3.3|17 15.26 cM Fgd2 0.00187656 2.2892NM_001123372 // Gm3435 // predicted gene 3435 // 17 A2|17 // 100041621 /// XM_006523370 Gm3435 1.23E-05 2.28881NM_178600 // Vkorc1 // vitamin K epoxide reductase complex, subunit 1 // 7 F3|7 69.81 c Vkorc1 2.18E-05 2.28806--- 0.00518008 2.28779NM_145401 // Prkag2 // protein kinase, AMP-activated, gamma 2 non-catalytic subunit // Prkag2 1.45E-05 2.28598NM_008986 // Ptrf // polymerase I and transcript release factor // 11 D|11 63.95 cM // Ptrf 0.000724049 2.28393NM_010820 // Mpdz // multiple PDZ domain protein // 4 C3|4 38.0 cM // 17475 /// ENSMUST Mpdz 0.000727872 2.28352NM_001080746 // Gtf2i // general transcription factor II I // 5 G2|5 74.48 cM // 14886 Gtf2i 0.000434897 2.28123NM_001081141 // Gabbr2 // gamma-aminobutyric acid (GABA) B receptor, 2 // 4 B1|4 // 242 Gabbr2 2.36E-05 2.28091NM_146041 // Gmds // GDP-mannose 4, 6-dehydratase // 13 A3.2|13 // 218138 /// ENSMUST00 Gmds 4.51E-05 2.28074NM_001171004 // Prkd3 // protein kinase D3 // 17 E3|17 // 75292 /// NM_029239 // Prkd3 Prkd3 3.24E-06 2.28016NM_133739 // Tmem123 // transmembrane protein 123 // 9 A1|9 // 71929 /// ENSMUST0000005 Tmem123 1.06E-06 2.27769NM_026514 // Cdc42ep3 // CDC42 effector protein (Rho GTPase binding) 3 // 17 E3|17 // 2 Cdc42ep3 9.52E-08 2.27709NM_008306 // Ndst1 // N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 1 // 18|1 Ndst1 1.24E-05 2.27691ENSMUST00000083425 // Gm23136 // predicted gene, 23136 // --- // --- Gm23136 0.00395714 2.27523ENSMUST00000098868 // 2610203C20Rik // RIKEN cDNA 2610203C20 gene // 9 A5.1|9 // 100042 2610203C20Rik 0.00302265 2.27467NM_181416 // Arhgap11a // Rho GTPase activating protein 11A // 2 E4|2 // 228482 /// ENS Arhgap11a 0.000125373 2.27185NM_133762 // Ncapg2 // non-SMC condensin II complex, subunit G2 // 12 F2|12 // 76044 // Ncapg2 9.20E-05 2.27074--- 0.001481 2.26984NM_001253706 // Sept6 // septin 6 // X|X A2 // 56526 /// ENSMUST00000053456 // Sept6 // Sep-06 0.000487891 2.26898NM_001081117 // Mki67 // antigen identified by monoclonal antibody Ki 67 // 7|7 F3-F5 / Mki67 0.00314163 2.26893NM_024188 // Oxct1 // 3-oxoacid CoA transferase 1 // 15 A1|15 // 67041 /// ENSMUST00000 Oxct1 6.27E-06 2.26863NM_001163513 // Dlg5 // discs, large homolog 5 (Drosophila) // 14 A3|14 // 71228 /// NM Dlg5 7.00E-06 2.26789NM_001205095 // Gm4944 // predicted gene 4944 // 17 A3.3|17 // 240038 /// XM_006524228 Gm4944 0.0012717 2.26771XM_006500510 // Stard9 // START domain containing 9 // 2 E5|2 // 668880 /// ENSMUST0000 Stard9 0.000155784 2.26637NM_026162 // Plxdc2 // plexin domain containing 2 // 2 A2-A3|2 // 67448 /// ENSMUST0000 Plxdc2 1.75E-06 2.26486NM_001110015 // Wdr36 // WD repeat domain 36 // 18 B1|18 // 225348 /// NM_001110016 // Wdr36 6.45E-06 2.2647NM_146089 // Haus1 // HAUS augmin-like complex, subunit 1 // 18 E3|18 // 225745 /// XM_ Haus1 0.000148878 2.26294NM_001039959 // Ahnak // AHNAK nucleoprotein (desmoyokin) // 19 A|19 // 66395 /// NM_00 Ahnak 3.16E-07 2.2623NM_001252525 // Cpeb1 // cytoplasmic polyadenylation element binding protein 1 // 7 D3| Cpeb1 0.0029661 2.26143NM_029556 // Clybl // citrate lyase beta like // 14 E5|14 // 69634 /// XM_006519497 // Clybl 0.000596884 2.25797NM_001290784 // Ldlrad3 // low density lipoprotein receptor class A domain containing 3 Ldlrad3 0.000382284 2.25548NM_007960 // Etv1 // ets variant 1 // 12 A3-B1|12 17.99 cM // 14009 /// XM_006514965 // Etv1 0.00176412 2.2532NM_009987 // Cx3cr1 // chemokine (C-X3-C motif) receptor 1 // 9 F4|9 // 13051 /// ENSMU Cx3cr1 0.000244349 2.25135NM_001030307 // Dkc1 // dyskeratosis congenita 1, dyskerin // X A7.3|X // 245474 /// EN Dkc1 0.000222363 2.25043NM_001081347 // Rhobtb1 // Rho-related BTB domain containing 1 // 10|10 B5.1 // 69288 / Rhobtb1 0.000333148 2.24762NM_001159559 // Xrcc6bp1 // XRCC6 binding protein 1 // 10 D3|10 // 68876 /// ENSMUST000 Xrcc6bp1 0.0017026 2.24711NM_198899 // Uggt1 // UDP-glucose glycoprotein glucosyltransferase 1 // 1 B|1 // 320011 Uggt1 1.37E-06 2.2455NM_001145824 // Hipk3 // homeodomain interacting protein kinase 3 // 2 E2|2 // 15259 // Hipk3 7.37E-06 2.24304NM_199029 // Zfp395 // zinc finger protein 395 // 14 D1|14 // 380912 /// ENSMUST0000006 Zfp395 0.00253512 2.24286NM_001113413 // Rnf13 // ring finger protein 13 // 3 D|3 // 24017 /// XM_006501457 // R Rnf13 1.08E-07 2.24123NM_138745 // Mthfd1 // methylenetetrahydrofolate dehydrogenase (NADP+ dependent), methe Mthfd1 0.000284431 2.24062NM_024191 // Arl2bp // ADP-ribosylation factor-like 2 binding protein // 8 C5|8 // 1075 Arl2bp 1.20E-07 2.23864NM_145398 // Casd1 // CAS1 domain containing 1 // 6 A1|6 1.81 cM // 213819 /// XM_00650 Casd1 8.45E-06 2.23843NM_152817 // Ttc27 // tetratricopeptide repeat domain 27 // 17 E2|17 // 74196 /// XM_00 Ttc27 0.000553869 2.23724NM_001001144 // Scap // SREBF chaperone // 9 F2|9 59.91 cM // 235623 /// NM_001103162 / Scap 3.29E-05 2.23654ENSMUST00000110991 // Slc12a6 // solute carrier family 12, member 6 // 2 E3|2 // 107723 Slc12a6 1.27E-07 2.23632--- 0.00082875 2.23271NM_001081201 // Dpy19l4 // dpy-19-like 4 (C. elegans) // 4 A1|4 // 381510 /// ENSMUST00 Dpy19l4 6.78E-06 2.22957NM_008397 // Itga6 // integrin alpha 6 // 2 C2-C3|2 42.79 cM // 16403 /// NM_001277970 Itga6 2.98E-05 2.22922NM_028964 // Snx29 // sorting nexin 29 // --- // 74478 /// ENSMUST00000122168 // Snx29 Snx29 0.0031073 2.22776NM_001008549 // Zfp658 // zinc finger protein 658 // 7 B4|7 // 210104 /// ENSMUST000001 Zfp658 0.00292333 2.22652NM_029870 // Crebrf // CREB3 regulatory factor // 17|17 B1 // 77128 /// XM_006525117 // Crebrf 0.000179891 2.22645NM_017391 // Slc5a3 // solute carrier family 5 (inositol transporters), member 3 // 16 Slc5a3 0.000316375 2.22617NM_177305 // Arl4c // ADP-ribosylation factor-like 4C // 1 D|1 // 320982 /// ENSMUST000 Arl4c 1.43E-05 2.22192NM_020010 // Cyp51 // cytochrome P450, family 51 // 5 A2|5 2.3 cM // 13121 /// ENSMUST0 Cyp51 1.69E-06 2.21677--- 0.00115168 2.21666NM_028428 // Fut11 // fucosyltransferase 11 // 14|14 B // 73068 /// ENSMUST00000048016 Fut11 2.88E-06 2.21105NM_001281929 // Gria3 // glutamate receptor, ionotropic, AMPA3 (alpha 3) // X A3.3-A4|X Gria3 0.000158145 2.21082NM_008960 // Pten // phosphatase and tensin homolog // 19 C1|19 28.14 cM // 19211 /// X Pten 4.23E-08 2.21042BC031701 // Cxx1c // CAAX box 1C // X A5|X // 72865 /// NM_028375 // Cxx1c // CAAX box Cxx1c 0.00126655 2.21037NM_007530 // Bcap29 // B cell receptor associated protein 29 // 12 A3|12 13.63 cM // 12 Bcap29 1.96E-05 2.21036ENSMUST00000082411 // ND3 // NADH dehydrogenase subunit 3 // --- // 17718 /// AK139029 ND3 0.000161048 2.20978NM_011234 // Rad51 // RAD51 homolog // 2 F1|2 59.92 cM // 19361 /// ENSMUST00000028795 Rad51 0.00494167 2.20863NM_018822 // Sgsh // N-sulfoglucosamine sulfohydrolase (sulfamidase) // 11 E2|11 83.36 Sgsh 9.05E-06 2.20801NM_153526 // Insig1 // insulin induced gene 1 // 5 B1|5 // 231070 /// ENSMUST0000005915 Insig1 3.52E-08 2.20787NM_001170395 // Cd163 // CD163 antigen // 6 F2|6 // 93671 /// NM_053094 // Cd163 // CD1 Cd163 6.01E-06 2.20589NM_001199321 // Zfp94 // zinc finger protein 94 // 7 A3|7 10.27 cM // 22756 /// NM_0095 Zfp94 0.000976954 2.20516--- 0.00297532 2.20284NM_001025570 // Prrx1 // paired related homeobox 1 // 1 H2.1|1 70.53 cM // 18933 /// NM Prrx1 4.69E-06 2.20218NM_023603 // Sfpq // splicing factor proline/glutamine rich (polypyrimidine tract bindi Sfpq 0.000104823 2.20127--- 0.000325586 2.20055

NM_001033145 // 1190002N15Rik // RIKEN cDNA 1190002N15 gene // 9 E3.3|9 // 68861 /// EN 1190002N15Rik 6.65E-05 2.20051NM_010124 // Eif4ebp2 // eukaryotic translation initiation factor 4E binding protein 2 Eif4ebp2 0.000251589 2.20011NM_153126 // Nat10 // N-acetyltransferase 10 // 2 E2|2 // 98956 /// XM_006500455 // Nat Nat10 7.42E-05 2.19992NR_028478 // Snora75 // small nucleolar RNA, H/ACA box 75 // 1|1 // 100303740 /// ENSMU Snora75 0.00517368 2.19983NM_001290662 // Kif2c // kinesin family member 2C // 4 D1|4 53.42 cM // 73804 /// NM_13 Kif2c 0.000108674 2.1993NM_026598 // Ebpl // emopamil binding protein-like // 14 D1|14 // 68177 /// ENSMUST0000 Ebpl 0.000135718 2.19863--- 0.00266185 2.19848ENSMUST00000082700 // Gm22620 // predicted gene, 22620 // --- // --- /// AK161656 // Ta Gm22620 0.00285274 2.19837NM_001081371 // Dmxl1 // Dmx-like 1 // 18 D1|18 // 240283 /// XM_006525916 // Dmxl1 // Dmxl1 3.31E-08 2.1981--- 0.0025695 2.19763NM_026880 // Pink1 // PTEN induced putative kinase 1 // 4 D3|4 // 68943 /// ENSMUST0000 Pink1 7.04E-06 2.19534NM_009773 // Bub1b // budding uninhibited by benzimidazoles 1 homolog, beta (S. cerevis Bub1b 0.00179251 2.1953NM_008152 // Gpr65 // G-protein coupled receptor 65 // 12 E|12 // 14744 /// ENSMUST0000 Gpr65 7.50E-07 2.19529ENSMUST00000000199 // Ncs1 // neuronal calcium sensor 1 // 2 B|2 // 14299 /// NM_019681 Ncs1 0.00417266 2.19495--- 4.19E-05 2.19375ENSMUST00000170447 // Rpl28-ps4 // ribosomal protein L28, pseudogene 4 // --- // --- Rpl28-ps4 0.00516546 2.19341NM_001081286 // Fat1 // FAT tumor suppressor homolog 1 (Drosophila) // 8 B1.1|8 24.81 c Fat1 5.93E-05 2.193NM_011156 // Prep // prolyl endopeptidase // 10 B2-B3|10 23.27 cM // 19072 /// ENSMUST0 Prep 1.97E-05 2.19081NM_172301 // Ccnb1 // cyclin B1 // 13 D1|13 53.23 cM // 268697 /// ENSMUST00000072119 / Ccnb1 0.00268129 2.18933--- 0.000811041 2.18805NM_001285991 // Tbc1d5 // TBC1 domain family, member 5 // 17 C|17 // 72238 /// NM_00128 Tbc1d5 2.86E-05 2.18792NM_001033219 // Slc45a4 // solute carrier family 45, member 4 // 15 D3|15 // 106068 /// Slc45a4 0.000761645 2.18587NM_028015 // Cers5 // ceramide synthase 5 // 15 F1|15 // 71949 /// ENSMUST00000023762 / Cers5 1.25E-05 2.18328--- 0.000401354 2.18292NM_001015039 // Zfyve28 // zinc finger, FYVE domain containing 28 // 5 B2|5 // 231125 / Zfyve28 0.000400408 2.18205NM_001110265 // Ttk // Ttk protein kinase // 9 E2|9 // 22137 /// NM_001284272 // Ttk // Ttk 0.000174356 2.18079--- 0.000247632 2.18048--- 0.000282871 2.17785NM_001122989 // Cdc14b // CDC14 cell division cycle 14B // 13 B3|13 // 218294 /// NM_17 Cdc14b 0.000186532 2.17624NM_029965 // Rnf170 // ring finger protein 170 // 8|8 // 77733 /// ENSMUST00000014022 / Rnf170 0.000737883 2.176--- 0.00312149 2.17423NM_027534 // Kdsr // 3-ketodihydrosphingosine reductase // 1 E2.1|1 // 70750 /// XM_006 Kdsr 0.000302972 2.17198NM_001199948 // Dynlt1f // dynein light chain Tctex-type 1F // 17 A1|17 // 100040531 Dynlt1f 2.34E-05 2.17097NM_023057 // Zak // sterile alpha motif and leucine zipper containing kinase AZK // 2 C Zak 9.01E-05 2.16974--- 0.00376839 2.16898XM_006515014 // Prkar2b // protein kinase, cAMP dependent regulatory, type II beta // 1 Prkar2b 2.15E-05 2.16892--- 4.58E-06 2.1684NM_001170643 // Rnf144b // ring finger protein 144B // 13 A5|13 // 218215 /// NM_146042 Rnf144b 0.00012184 2.16832NM_001081323 // Mphosph9 // M-phase phosphoprotein 9 // 5 F|5 // 269702 /// NM_00127786 Mphosph9 0.000101386 2.16744NM_001081081 // Gls // glutaminase // 1 C1.1|1 26.86 cM // 14660 /// NM_001113383 // Gl Gls 1.09E-05 2.1665NM_025780 // Thap2 // THAP domain containing, apoptosis associated protein 2 // 10 D2|1 Thap2 0.00464203 2.16592ENSMUST00000104252 // Gm23130 // predicted gene, 23130 // --- // --- Gm23130 0.000474403 2.16508NM_001164733 // Mpp6 // membrane protein, palmitoylated 6 (MAGUK p55 subfamily member 6 Mpp6 3.61E-05 2.16492NM_001167885 // Suv420h1 // suppressor of variegation 4-20 homolog 1 (Drosophila) // 19 Suv420h1 1.08E-05 2.16469NM_001271407 // Sorbs3 // sorbin and SH3 domain containing 3 // 14 D2|14 36.27 cM // 20 Sorbs3 0.000542185 2.16458NM_001008502 // Bbs12 // Bardet-Biedl syndrome 12 (human) // 3 B|3 // 241950 /// NM_001 Bbs12 0.00374185 2.16138XM_006510240 // Gramd1b // GRAM domain containing 1B // 9|9 B // 235283 /// NM_172768 / Gramd1b 6.20E-06 2.15975NM_011273 // Xpr1 // xenotropic and polytropic retrovirus receptor 1 // 1 G3|1 66.49 cM Xpr1 6.82E-07 2.15883NM_144915 // Daglb // diacylglycerol lipase, beta // 5 G2|5 // 231871 /// XM_006504699 Daglb 1.67E-06 2.15831--- 0.000390739 2.15687NM_012056 // Fkbp9 // FK506 binding protein 9 // 6 B3|6 27.74 cM // 27055 /// ENSMUST00 Fkbp9 1.54E-05 2.15616--- 0.000260041 2.15345NM_025969 // Timm21 // tranlocase of inner mitochondrial membrane 21 // 18|18 E3 // 671 Timm21 0.0022304 2.15309NM_025277 // Gng10 // guanine nucleotide binding protein (G protein), gamma 10 // 4 B3| Gng10 1.13E-05 2.15284NM_022315 // Smoc2 // SPARC related modular calcium binding 2 // 17 A2|17 8.95 cM // 64 Smoc2 0.00448854 2.15175NM_010008 // Cyp2j6 // cytochrome P450, family 2, subfamily j, polypeptide 6 // 4 C5|4 Cyp2j6 0.00139978 2.15049NR_045098 // Gm2115 // predicted gene 2115 // 7 D3|7 // 100039239 /// ENSMUST0000018038 Gm2115 0.00287242 2.14913NM_010111 // Efnb2 // ephrin B2 // 8 A1.1|8 3.42 cM // 13642 /// ENSMUST00000001319 // Efnb2 0.00315312 2.14815NM_001162375 // Fam73a // family with sequence similarity 73, member A // 3 H3|3 // 215 Fam73a 0.000861726 2.14593NM_028149 // Fbxl20 // F-box and leucine-rich repeat protein 20 // 11 D|11 // 72194 /// Fbxl20 5.55E-05 2.14228NM_013589 // Ltbp2 // latent transforming growth factor beta binding protein 2 // 12|12 Ltbp2 0.000139572 2.14213NM_175518 // Tmem245 // transmembrane protein 245 // 4 B3|4 // 242474 /// ENSMUST000000 Tmem245 7.48E-05 2.14151NM_001033458 // Gm1673 // predicted gene 1673 // 5 B2|5 // 381633 /// ENSMUST0000009486 Gm1673 0.000353308 2.14124NM_001146707 // Nap1l1 // nucleosome assembly protein 1-like 1 // 10 D1|10 58.67 cM // Nap1l1 1.69E-06 2.14026NM_172882 // Wdfy3 // WD repeat and FYVE domain containing 3 // 5 E4-E5|5 48.95 cM // 7 Wdfy3 1.14E-06 2.13995NM_133818 // AI597479 // expressed sequence AI597479 // 1 B|1 // 98404 /// ENSMUST00000 AI597479 0.00269686 2.13982--- 0.000531482 2.13955NM_181547 // Nostrin // nitric oxide synthase trafficker // 2 C2|2 // 329416 /// ENSMUS Nostrin 6.22E-06 2.13918--- 0.000129176 2.13807NM_001163687 // Naaa // N-acylethanolamine acid amidase // 5|5 E3 // 67111 /// NM_02597 Naaa 1.06E-06 2.13799NM_007496 // Zfhx3 // zinc finger homeobox 3 // 8|8 E1 // 11906 /// XM_006530586 // Zfh Zfhx3 0.000176886 2.13767NM_175445 // Rassf2 // Ras association (RalGDS/AF-6) domain family member 2 // 2 F2|2 / Rassf2 3.08E-06 2.13656NR_028401 // Taf1d // TATA box binding protein (Tbp)-associated factor, RNA polymerase Taf1d 0.000170675 2.136--- 0.000458928 2.13383--- 0.00451048 2.1338NM_027903 // Dhdh // dihydrodiol dehydrogenase (dimeric) // 7 B2|7 29.32 cM // 71755 // Dhdh 4.93E-07 2.13358NM_001159536 // Adcy3 // adenylate cyclase 3 // 12|12 A-B // 104111 /// NM_001159537 // Adcy3 0.00199641 2.1331NR_015597 // Zfp862-ps // zinc finger protein 862, pseudogene // 6 B2.3|6 // 58894 /// Zfp862-ps 0.00265644 2.13194NM_028319 // Zfp518a // zinc finger protein 518A // 19 D1|19 // 72672 /// ENSMUST000000 Zfp518a 5.25E-05 2.13129NM_001159516 // Qk // quaking // 17 A1|17 7.75 cM // 19317 /// NM_001159517 // Qk // qu Qk 3.37E-06 2.13032NM_172437 // Pus7l // pseudouridylate synthase 7 homolog (S. cerevisiae)-like // 15 E3| Pus7l 0.000105359 2.13016NM_028102 // Ddhd2 // DDHD domain containing 2 // 8|8 A3 // 72108 /// XR_378791 // Ddhd Ddhd2 5.34E-05 2.12891ENSMUST00000129570 // Gm11974 // predicted gene 11974 // --- // --- /// AK160548 // Gm1 Gm11974 0.000714235 2.12665NR_029382 // Mir17hg // Mir17 host gene 1 (non-protein coding) // 14|14 // 75957 /// NR Mir17hg 0.000866475 2.12661NM_009128 // Scd2 // stearoyl-Coenzyme A desaturase 2 // 19 C3|19 37.98 cM // 20250 /// Scd2 3.14E-08 2.12654NM_011159 // Prkdc // protein kinase, DNA activated, catalytic polypeptide // 16 10.09 Prkdc 0.000110209 2.12582--- 0.00455781 2.12567--- 0.00216441 2.12357NM_029999 // Lbh // limb-bud and heart // 17 E2|17 // 77889 /// ENSMUST00000024857 // L Lbh 1.20E-05 2.12312NM_146019 // Chd3 // chromodomain helicase DNA binding protein 3 // 11 B3|11 // 216848 Chd3 0.0042899 2.11994NM_028906 // Dpp8 // dipeptidylpeptidase 8 // 9|9 D // 74388 /// XM_006511517 // Dpp8 / Dpp8 1.53E-06 2.11931NM_025382 // Tmem57 // transmembrane protein 57 // 4 D3|4 67.11 cM // 66146 /// ENSMUST Tmem57 2.04E-05 2.11894NM_001001985 // Nat8l // N-acetyltransferase 8-like // 5 B2|5 // 269642 /// ENSMUST0000 Nat8l 0.0013404 2.11662NM_011467 // Spr // sepiapterin reductase // 6 C3|6 37.15 cM // 20751 /// ENSMUST000000 Spr 0.0039973 2.11591NM_012012 // Exo1 // exonuclease 1 // 1 H4|1 81.9 cM // 26909 /// XM_006496862 // Exo1 Exo1 0.000757033 2.11558

NM_001267622 // Ttc28 // tetratricopeptide repeat domain 28 // 5 F|5 // 209683 /// ENSM Ttc28 0.000556522 2.11512NM_001290514 // Mospd1 // motile sperm domain containing 1 // X|X A4 // 70380 /// NM_02 Mospd1 7.97E-07 2.11453NM_007564 // Zfp36l1 // zinc finger protein 36, C3H type-like 1 // 12 C3|12 // 12192 // Zfp36l1 7.41E-05 2.11272--- 5.74E-05 2.11238NM_148945 // Rps6ka3 // ribosomal protein S6 kinase polypeptide 3 // X F4|X 73.27 cM // Rps6ka3 8.20E-06 2.11078NM_016681 // Chek2 // checkpoint kinase 2 // 5 F|5 // 50883 /// XM_006535068 // Chek2 / Chek2 0.000178994 2.11004NM_001285997 // Prc1 // protein regulator of cytokinesis 1 // 7 D3|7 45.62 cM // 233406 Prc1 0.000235381 2.10943NM_182997 // Prkab2 // protein kinase, AMP-activated, beta 2 non-catalytic subunit // 3 Prkab2 0.000461987 2.10769NM_001162904 // Mdm1 // transformed mouse 3T3 cell double minute 1 // 10 C1-C3|10 66.65 Mdm1 0.000499884 2.10714NM_030133 // Srbd1 // S1 RNA binding domain 1 // 17 E4|17 // 78586 /// ENSMUST000000951 Srbd1 0.00508915 2.10677NM_146126 // Sord // sorbitol dehydrogenase // 2 E5|2 60.59 cM // 20322 /// ENSMUST0000 Sord 4.12E-06 2.10555NM_175563 // Prr11 // proline rich 11 // 11 C|11 // 270906 /// ENSMUST00000051395 // Pr Prr11 0.00219805 2.10492NM_173444 // Nbeal1 // neurobeachin like 1 // 1 C2|1 // 269198 /// XM_006496031 // Nbea Nbeal1 0.000114463 2.10406ENSMUST00000180411 // Gm17491 // predicted gene, 17491 // 8|8 11.42 cM // 100502938 Gm17491 5.97E-05 2.10345NM_001005510 // Syne2 // spectrin repeat containing, nuclear envelope 2 // 12 C3|12 33. Syne2 0.000796387 2.10281NM_207541 // Zfp81 // zinc finger protein 81 // 17 B1|17 // 224694 /// ENSMUST000000540 Zfp81 0.00523404 2.10174NM_001177751 // Tsc22d1 // TSC22 domain family, member 1 // 14 D3|14 40.44 cM // 21807 Tsc22d1 5.13E-06 2.10073NM_001193271 // Meis1 // Meis homeobox 1 // 11 A3.1|11 11.11 cM // 17268 /// NM_010789 Meis1 0.00132608 2.10071--- 0.00276662 2.10013NM_019413 // Robo1 // roundabout homolog 1 (Drosophila) // 16 C3.1|16 // 19876 /// XM_0 Robo1 0.000411718 2.09966NM_021510 // Hnrnph1 // heterogeneous nuclear ribonucleoprotein H1 // 11|11 B1.2 // 590 Hnrnph1 6.86E-05 2.09866NM_001164046 // Gm13306 // predicted gene 13306 // 4 A5|4 // 100039863 /// NM_001199959 Gm13306 0.00208759 2.09688NM_001111324 // Nedd9 // neural precursor cell expressed, developmentally down-regulate Nedd9 0.00014849 2.09655NM_001081960 // Clasp2 // CLIP associating protein 2 // 9|9 F2 // 76499 /// NM_00111434 Clasp2 7.16E-06 2.09644NM_001271413 // Nfam1 // Nfat activating molecule with ITAM motif 1 // 15|15 E2 // 7403 Nfam1 8.33E-05 2.09175NM_134012 // Mbtd1 // mbt domain containing 1 // 11 D|11 // 103537 /// XM_006531889 // Mbtd1 0.000264142 2.08955NM_009530 // Atrx // alpha thalassemia/mental retardation syndrome X-linked homolog (hu Atrx 1.28E-05 2.08929NM_144908 // Galnt11 // UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactos Galnt11 7.74E-05 2.08889NM_030732 // Tbl1xr1 // transducin (beta)-like 1X-linked receptor 1 // 3 A3|3 // 81004 Tbl1xr1 0.00018273 2.08761NM_029617 // Casc5 // cancer susceptibility candidate 5 // 2 E5|2 // 76464 /// ENSMUST0 Casc5 0.00299821 2.08624NM_011086 // Pikfyve // phosphoinositide kinase, FYVE finger containing // 1 C2|1 // 18 Pikfyve 3.69E-06 2.08579NM_025626 // Fam107b // family with sequence similarity 107, member B // 2 A1|2 // 6654 Fam107b 0.00018985 2.08375NM_134042 // Aldh6a1 // aldehyde dehydrogenase family 6, subfamily A1 // 12 D1|12 39.21 Aldh6a1 8.18E-05 2.08343NM_020270 // Scamp5 // secretory carrier membrane protein 5 // 9 B|9 // 56807 /// XM_00 Scamp5 0.000699976 2.08239NM_011101 // Prkca // protein kinase C, alpha // 11 E1|11 70.8 cM // 18750 /// ENSMUST0 Prkca 6.62E-07 2.08135NM_025377 // Ska2 // spindle and kinetochore associated complex subunit 2 // 11 C|11 // Ska2 0.00114395 2.08095NM_011699 // Lin7c // lin-7 homolog C (C. elegans) // 2 E3|2 56.65 cM // 22343 /// ENSM Lin7c 1.51E-05 2.08081NM_027144 // Arhgef12 // Rho guanine nucleotide exchange factor (GEF) 12 // 9|9 B // 69 Arhgef12 1.45E-05 2.0804NM_026579 // D10Wsu102e // DNA segment, Chr 10, Wayne State University 102, expressed / D10Wsu102e 0.000218028 2.07971NM_172779 // Ddx26b // DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 26B // X A5|X // 23 Ddx26b 0.0013386 2.07885NM_009142 // Cx3cl1 // chemokine (C-X3-C motif) ligand 1 // 8 C5|8 46.79 cM // 20312 // Cx3cl1 0.00530959 2.07866NM_011391 // Slc16a7 // solute carrier family 16 (monocarboxylic acid transporters), me Slc16a7 3.54E-06 2.07797--- 0.00318876 2.07791NM_175751 // Zfp608 // zinc finger protein 608 // 18 D3|18 // 269023 /// ENSMUST0000006 Zfp608 0.00517537 2.07675NM_145437 // Cd300ld // CD300 molecule-like family member d // 11 E2|11 // 217305 /// E Cd300ld 5.60E-05 2.0767NM_007691 // Chek1 // checkpoint kinase 1 // 9|9 A5.3 // 12649 /// ENSMUST00000034625 / Chek1 0.00289499 2.07619NM_001252494 // Rapgef6 // Rap guanine nucleotide exchange factor (GEF) 6 // 11 B1.3|11 Rapgef6 0.000200745 2.07606NM_009128 // Scd2 // stearoyl-Coenzyme A desaturase 2 // 19 C3|19 37.98 cM // 20250 /// Scd2 0.000176755 2.07591NM_028749 // Npl // N-acetylneuraminate pyruvate lyase // 1|1 G2 // 74091 /// ENSMUST00 Npl 0.0006051 2.07486NM_053122 // Immp2l // IMP2 inner mitochondrial membrane peptidase-like (S. cerevisiae) Immp2l 0.00300827 2.07454NM_001162416 // Pfkfb2 // 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 // 1 E4 Pfkfb2 0.000178318 2.07422NM_172307 // Mbtps2 // membrane-bound transcription factor peptidase, site 2 // X F4|X Mbtps2 6.53E-05 2.07258NM_001042421 // Kntc1 // kinetochore associated 1 // 5 F|5 // 208628 /// XM_006530250 / Kntc1 0.000446337 2.07247NM_172467 // Zc3hav1l // zinc finger CCCH-type, antiviral 1-like // 6 B1|6 // 209032 // Zc3hav1l 0.00194388 2.07066--- 0.000986138 2.0699NM_013552 // Hmmr // hyaluronan mediated motility receptor (RHAMM) // 11 A5|11 24.4 cM Hmmr 0.00025175 2.06967ENSMUST00000046303 // Crebl2 // cAMP responsive element binding protein-like 2 // 6 G1| Crebl2 0.00211861 2.06864NM_027906 // Vwa8 // von Willebrand factor A domain containing 8 // 14 D3|14 // 219189 Vwa8 1.15E-05 2.06812NM_177660 // Zbtb10 // zinc finger and BTB domain containing 10 // 3 A1|3 // 229055 /// Zbtb10 0.000133695 2.06786NM_011313 // S100a6 // S100 calcium binding protein A6 (calcyclin) // 3 F1-F2|3 39.35 c S100a6 7.23E-05 2.06768ENSMUST00000173858 // Efr3a // EFR3 homolog A (S. cerevisiae) // 15 D1|15 // 76740 /// Efr3a 0.000197226 2.06501NM_026570 // Yeats4 // YEATS domain containing 4 // 10 D2|10 // 64050 /// ENSMUST000000 Yeats4 6.65E-05 2.06486NM_030697 // Kank3 // KN motif and ankyrin repeat domains 3 // 17 B1|17 17.98 cM // 808 Kank3 0.000506218 2.06293NR_037666 // Gm16861 // predicted gene, 16861 // 16|16 2.48 cM // 100503704 /// ENSMUST Gm16861 0.00027841 2.06042NM_008873 // Plau // plasminogen activator, urokinase // 14 A3|14 11.53 cM // 18792 /// Plau 5.46E-05 2.06007NM_019438 // Ncapg // non-SMC condensin I complex, subunit G // 5 B3|5 // 54392 /// XR_ Ncapg 0.00503321 2.05957NM_007459 // Ap2a2 // adaptor-related protein complex 2, alpha 2 subunit // 7 F5|7 // 1 Ap2a2 3.28E-07 2.05808NM_001033336 // Abcc4 // ATP-binding cassette, sub-family C (CFTR/MRP), member 4 // 14 Abcc4 0.000107389 2.05617NM_013935 // Ptpla // protein tyrosine phosphatase-like (proline instead of catalytic a Ptpla 0.000241228 2.05583XR_388930 // LOC102635561 // uncharacterized LOC102635561 // --- // 102635561 /// XR_39 LOC102635561 0.000177537 2.05579--- 0.000832334 2.05465NM_001081238 // Palb2 // partner and localizer of BRCA2 // 7 F3|7 // 233826 /// ENSMUST Palb2 0.00316914 2.05431ENSMUST00000105868 // Stmn1 // stathmin 1 // 4 D3|4 66.76 cM // 16765 /// NM_019641 // Stmn1 0.00167382 2.05344XM_006516362 // Nubpl // nucleotide binding protein-like // 12 C1|12 // 76826 /// XM_00 Nubpl 0.00349325 2.05301--- 0.000966077 2.05243NM_001159572 // 4632428N05Rik // RIKEN cDNA 4632428N05 gene // 10 B4|10 // 74048 /// NM 4632428N05Rik 4.44E-06 2.0524NM_029600 // Abcc3 // ATP-binding cassette, sub-family C (CFTR/MRP), member 3 // 11 D|1 Abcc3 4.74E-07 2.052NM_029938 // H2afv // H2A histone family, member V // 11 A1|11 // 77605 /// ENSMUST0000 H2afv 0.00057191 2.05185NM_138753 // Hexim1 // hexamethylene bis-acetamide inducible 1 // 11 E1|11 // 192231 // Hexim1 2.71E-05 2.0501NM_029492 // Zdhhc20 // zinc finger, DHHC domain containing 20 // 14 C3|14 // 75965 /// Zdhhc20 8.08E-05 2.04974NM_146261 // Fam199x // family with sequence similarity 199, X-linked // X F1|X // 2456 Fam199x 0.000240685 2.04778AK131743 // Gm10572 // predicted gene 10572 // 4 D2.2|4 // 100038647 Gm10572 0.00122065 2.04759ENSMUST00000183421 // Trps1 // trichorhinophalangeal syndrome I (human) // 15 C|15 19.1 Trps1 9.40E-05 2.04729NM_181584 // Gab3 // growth factor receptor bound protein 2-associated protein 3 // X A Gab3 0.00113524 2.04721NM_019993 // Aldh9a1 // aldehyde dehydrogenase 9, subfamily A1 // 1|1 H2 // 56752 /// X Aldh9a1 5.95E-06 2.04414ENSMUST00000083297 // Gm22972 // predicted gene, 22972 // --- // --- /// ENSMUST0000014 Gm22972 2.00E-05 2.04372--- 0.00445071 2.04366NM_009149 // Glg1 // golgi apparatus protein 1 // 8 E1|8 57.98 cM // 20340 /// ENSMUST0 Glg1 1.01E-05 2.04322NM_001081212 // Irs2 // insulin receptor substrate 2 // 8 A1.1|8 5.35 cM // 384783 /// Irs2 0.00258127 2.04278--- 0.000156326 2.04267NM_001285463 // Carf // calcium response factor // 1 C2|1 // 241066 /// NM_001285473 // Carf 0.00152926 2.04243NM_153587 // Rps6ka5 // ribosomal protein S6 kinase, polypeptide 5 // 12 E|12 // 73086 Rps6ka5 0.000855821 2.04236NM_172700 // Zmpste24 // zinc metallopeptidase, STE24 // 4 D2.2|4 // 230709 /// ENSMUST Zmpste24 9.34E-05 2.04188NM_027188 // Smyd3 // SET and MYND domain containing 3 // 1 H3|1 83.48 cM // 69726 /// Smyd3 8.05E-05 2.04172--- 0.0024524 2.04133

NM_001164624 // Zfp809 // zinc finger protein 809 // 9 A3|9 // 235047 /// NM_172763 // Zfp809 0.000157616 2.04074NM_011035 // Pak1 // p21 protein (Cdc42/Rac)-activated kinase 1 // 7 E2|7 53.57 cM // 1 Pak1 7.95E-06 2.04073NM_007790 // Smc3 // structural maintenance of chromosomes 3 // 19 D2|19 // 13006 /// E Smc3 4.71E-06 2.04009NM_027810 // Bbs7 // Bardet-Biedl syndrome 7 (human) // 3 B|3 // 71492 /// ENSMUST00000 Bbs7 0.000341261 2.03995NM_026189 // Eepd1 // endonuclease/exonuclease/phosphatase family domain containing 1 / Eepd1 5.90E-05 2.03723NM_019549 // Plek // pleckstrin // 11 A2|11 9.41 cM // 56193 /// ENSMUST00000102881 // Plek 0.000337069 2.03672NM_026174 // Entpd4 // ectonucleoside triphosphate diphosphohydrolase 4 // 14 D2|14 // Entpd4 1.37E-08 2.03542NM_207659 // Hook3 // hook homolog 3 (Drosophila) // 8 A2|8 // 320191 /// XM_006509149 Hook3 1.03E-06 2.03449NM_026796 // Smyd2 // SET and MYND domain containing 2 // 1 H6|1 // 226830 /// XM_00649 Smyd2 0.000564274 2.03372ENSMUST00000082411 // ND3 // NADH dehydrogenase subunit 3 // --- // 17718 /// AK139029 ND3 6.43E-06 2.03307NM_178143 // Prkaa2 // protein kinase, AMP-activated, alpha 2 catalytic subunit // 4 C6 Prkaa2 0.000310474 2.03078NM_025863 // Trim59 // tripartite motif-containing 59 // 3|3 E2 // 66949 /// ENSMUST000 Trim59 0.00106218 2.02981NM_145456 // Zswim6 // zinc finger SWIM-type containing 6 // 13 D2.1|13 // 67263 /// EN Zswim6 9.32E-05 2.02917ENSMUST00000041659 // Prrx2 // paired related homeobox 2 // 2 B|2 21.74 cM // 20204 /// Prrx2 0.000396742 2.02907NM_025693 // Tmem41a // transmembrane protein 41a // 16 B1|16 // 66664 /// NR_037773 // Tmem41a 0.000616502 2.0285NM_001164503 // Akap11 // A kinase (PRKA) anchor protein 11 // 14 D3|14 // 219181 /// E Akap11 0.000427388 2.02706NM_199198 // Hdac10 // histone deacetylase 10 // 15 E3|15 // 170787 /// NR_028447 // Hd Hdac10 0.00235608 2.02685NM_008212 // Hadh // hydroxyacyl-Coenzyme A dehydrogenase // 3 G3|3 // 15107 /// ENSMUS Hadh 9.38E-05 2.02643NR_046048 // Gm10677 // predicted gene 10677 // --- // 100038460 Gm10677 0.00030983 2.0257NM_001038621 // Rabgap1l // RAB GTPase activating protein 1-like // 1 H2.1|1 // 29809 / Rabgap1l 0.000597479 2.02533NM_001205369 // Casc4 // cancer susceptibility candidate 4 // 2 E5|2 // 319996 /// NM_0 Casc4 0.00496106 2.02116NM_008021 // Foxm1 // forkhead box M1 // 6 F3|6 62.98 cM // 14235 /// ENSMUST0000007331 Foxm1 0.00190442 2.01964NM_080288 // Elmo1 // engulfment and cell motility 1 // 13|13 A3.1 // 140580 /// NM_198 Elmo1 1.14E-05 2.01922XR_374487 // Knstrn // kinetochore-localized astrin/SPAG5 binding // 2 E5|2 // 51944 // Knstrn 0.00031995 2.01769NM_029306 // 1700012B09Rik // RIKEN cDNA 1700012B09 gene // 9 A2|9 // 69325 /// XR_3791 1700012B09Rik 0.00140795 2.01518NR_040556 // Gm6634 // predicted gene 6634 // 3 E2|3 // 625901 /// ENSMUST00000180497 / Gm6634 0.000704484 2.01508NM_001083334 // Bin1 // bridging integrator 1 // 18 B1|18 18.01 cM // 30948 /// NM_0096 Bin1 3.97E-06 2.01466--- 0.000636952 2.01316NM_009796 // Capn7 // calpain 7 // 14 B|14 // 12339 /// ENSMUST00000022451 // Capn7 // Capn7 2.79E-05 2.01188NM_001033155 // Dnajb14 // DnaJ (Hsp40) homolog, subfamily B, member 14 // 3 G3|3 // 70 Dnajb14 4.30E-06 2.01173ENSMUST00000112103 // Nav1 // neuron navigator 1 // --- // --- /// AK158038 // Nav1 // Nav1 0.00522844 2.01147NM_001015681 // E130308A19Rik // RIKEN cDNA E130308A19 gene // 4 B3|4 // 230259 /// NM_ E130308A19Rik 0.000637824 2.01105NM_011992 // Rcn2 // reticulocalbin 2 // 9|9 C // 26611 /// ENSMUST00000114276 // Rcn2 Rcn2 8.17E-07 2.00982NM_001110195 // Echdc1 // enoyl Coenzyme A hydratase domain containing 1 // 10 A4|10 16 Echdc1 0.000103404 2.00971NM_028320 // Adipor1 // adiponectin receptor 1 // 1 E4|1 // 72674 /// ENSMUST0000002772 Adipor1 1.77E-06 2.00947ENSMUST00000148876 // Mettl8 // methyltransferase like 8 // 2 C2|2 // 228019 /// NM_001 Mettl8 0.00105169 2.00934NM_008961 // Pter // phosphotriesterase related // 2 A1|2 // 19212 /// XM_006497400 // Pter 0.000458353 2.00876NM_008737 // Nrp1 // neuropilin 1 // 8 E|8 75.78 cM // 18186 /// ENSMUST00000026917 // Nrp1 1.64E-05 2.00795NR_045008 // Gm20300 // predicted gene, 20300 // 10|10 17.1 cM // 100504586 Gm20300 0.00363361 2.00788NM_011218 // Ptprs // protein tyrosine phosphatase, receptor type, S // 17 D|17 29.32 c Ptprs 0.00193437 2.00758NM_010499 // Ier2 // immediate early response 2 // 8 C3|8 41.02 cM // 15936 /// ENSMUST Ier2 8.59E-06 2.00626NM_144918 // Smyd5 // SET and MYND domain containing 5 // 6 C3|6 37.44 cM // 232187 /// Smyd5 2.40E-05 2.00593NM_199476 // Rrm2b // ribonucleotide reductase M2 B (TP53 inducible) // 15 B3.1|15 // 3 Rrm2b 0.000136839 2.00529NM_011623 // Top2a // topoisomerase (DNA) II alpha // 11 D|11 62.91 cM // 21973 /// ENS Top2a 6.10E-05 2.00525NM_153153 // Svil // supervillin // 18 A1|18 // 225115 /// XM_006525793 // Svil // supe Svil 0.000429031 2.00512NM_001076789 // Cbx5 // chromobox 5 // 15 F3|15 // 12419 /// NM_001110216 // Cbx5 // ch Cbx5 3.46E-05 2.00408NM_001159365 // Cep97 // centrosomal protein 97 // 16 C1.1|16 // 74201 /// NM_001159366 Cep97 0.00233242 2.00377NM_133829 // Mfsd6 // major facilitator superfamily domain containing 6 // 1 C1.1|1 // Mfsd6 9.11E-05 2.00248NR_015585 // 4933439C10Rik // RIKEN cDNA 4933439C10 gene // 11 B1.3|11 // 74476 /// ENS 4933439C10Rik 0.00080427 2.00238NM_144877 // Mettl13 // methyltransferase like 13 // 1|1 H1 // 71449 /// ENSMUST0000002 Mettl13 0.00299739 2.00049NM_001167883 // Ankrd50 // ankyrin repeat domain 50 // 3 B|3 // 99696 /// ENSMUST000001 Ankrd50 1.49E-05 -2.00037NM_001048054 // Dusp16 // dual specificity phosphatase 16 // 6 G1|6 65.77 cM // 70686 / Dusp16 0.00037141 -2.00129NM_013562 // Ifrd1 // interferon-related developmental regulator 1 // 12 B1|12 18.06 cM Ifrd1 3.23E-05 -2.00175NM_021449 // Crbn // cereblon // 6 E2|6 // 58799 /// NM_175357 // Crbn // cereblon // 6 Crbn 5.64E-07 -2.00461--- 0.0040079 -2.0055NM_031257 // Plekha2 // pleckstrin homology domain-containing, family A (phosphoinositi Plekha2 7.01E-06 -2.00581NM_015797 // Fbxo6 // F-box protein 6 // 4 E2|4 78.67 cM // 50762 /// ENSMUST0000010570 Fbxo6 3.38E-05 -2.00631NM_175687 // A230050P20Rik // RIKEN cDNA A230050P20 gene // 9 A3|9 // 319278 /// ENSMUS A230050P20Rik 0.000660084 -2.00667NM_133816 // Sh3bp4 // SH3-domain binding protein 4 // 1 D|1 // 98402 /// ENSMUST000000 Sh3bp4 0.000437284 -2.0073NM_054041 // Antxr1 // anthrax toxin receptor 1 // 6 D1|6 // 69538 /// XM_006506564 // Antxr1 3.56E-06 -2.00761NM_025653 // 3110001I22Rik // RIKEN cDNA 3110001I22 gene // 16 A1|16 // 66598 /// NM_02 3110001I22Rik 5.52E-05 -2.01109NM_001077684 // Ccdc173 // coiled-coil domain containing 173 // 2 C2|2 // 75051 /// ENS Ccdc173 0.000997558 -2.01157--- 3.86E-05 -2.01202--- 0.00135178 -2.01526NM_001039103 // Rasa4 // RAS p21 protein activator 4 // 5 G2|5 // 54153 /// NM_133914 / Rasa4 0.000139785 -2.01725ENSMUST00000103694 // Traj49 // T cell receptor alpha joining 49 // --- // --- /// AK13 Traj49 0.000807816 -2.01729ENSMUST00000015812 // Pdzd11 // PDZ domain containing 11 // X C3|X // 72621 /// ENSMUST Pdzd11 6.61E-05 -2.02023NM_009401 // Tnfrsf8 // tumor necrosis factor receptor superfamily, member 8 // 4 E1|4 Tnfrsf8 0.00501895 -2.02059XR_380941 // LOC102633407 // uncharacterized LOC102633407 // --- // 102633407 /// ENSMU LOC102633407 0.000175127 -2.02143NM_001291003 // Astl // astacin-like metalloendopeptidase (M12 family) // 2|2 F // 2150 Astl 0.000161339 -2.02154NM_001291358 // Pgap2 // post-GPI attachment to proteins 2 // 7 E3|7 // 233575 /// NM_1 Pgap2 1.53E-05 -2.0221--- 0.000207731 -2.02329NM_001201341 // Msi2 // musashi RNA-binding protein 2 // 11 C|11 // 76626 /// NM_054043 Msi2 0.000463308 -2.02419NM_145584 // Spon1 // spondin 1, (f-spondin) extracellular matrix protein // 7 F1|7 // Spon1 0.00126488 -2.02523NM_019788 // Bloc1s6 // biogenesis of lysosomal organelles complex-1, subunit 6, pallid Bloc1s6 4.03E-05 -2.02703NM_001098789 // Ndufa4l2 // NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like Ndufa4l2 0.0025229 -2.02808NM_001163430 // Sirt6 // sirtuin 6 // 10 C1|10 39.72 cM // 50721 /// XM_006513861 // Si Sirt6 0.000743268 -2.03189ENSMUST00000122606 // Gm25270 // predicted gene, 25270 // --- // --- Gm25270 0.000351397 -2.03268NM_001277255 // Acvrl1 // activin A receptor, type II-like 1 // 15|15 F3 // 11482 /// N Acvrl1 8.16E-06 -2.03454ENSMUST00000171380 // Gm17337 // predicted gene, 17337 // --- // --- Gm17337 0.000603382 -2.03645NM_197986 // Tmem140 // transmembrane protein 140 // 6 B1|6 // 68487 /// XM_006506540 / Tmem140 2.46E-06 -2.03757NM_007808 // Cycs // cytochrome c, somatic // 6 B2.3|6 24.32 cM // 13063 /// ENSMUST000 Cycs 0.00129803 -2.03764NM_007808 // Cycs // cytochrome c, somatic // 6 B2.3|6 24.32 cM // 13063 /// ENSMUST000 Cycs 0.00129803 -2.03764NM_001025313 // Tapbp // TAP binding protein // 17 B1|17 17.98 cM // 21356 /// NM_00931 Tapbp 1.96E-05 -2.03881NM_001252593 // Cars // cysteinyl-tRNA synthetase // 7 F5|7 88.25 cM // 27267 /// NM_01 Cars 0.000165959 -2.03997NM_001002005 // Panx2 // pannexin 2 // 15E3|15 // 406218 /// XM_006521139 // Panx2 // p Panx2 4.63E-05 -2.04156NM_001252503 // Aftph // aftiphilin // 11 A3.1|11 // 216549 /// NM_001290545 // Aftph / Aftph 0.000305871 -2.04182NM_001190817 // Dnajc1 // DnaJ (Hsp40) homolog, subfamily C, member 1 // 2|2 A2 // 1341 Dnajc1 0.000134747 -2.04389NM_153570 // Noc4l // nucleolar complex associated 4 homolog (S. cerevisiae) // 5 F|5 / Noc4l 4.95E-08 -2.04495NM_011596 // Atp6v0a2 // ATPase, H+ transporting, lysosomal V0 subunit A2 // 5 F|5 // 2 Atp6v0a2 1.94E-08 -2.04641NM_001033534 // Layn // layilin // 9 A5.3|9 // 244864 /// ENSMUST00000098782 // Layn // Layn 1.21E-05 -2.04676NM_011581 // Thbs2 // thrombospondin 2 // 17 A3-B|17 8.95 cM // 21826 /// ENSMUST000001 Thbs2 0.00256675 -2.04711ENSMUST00000180613 // Gdap10 // ganglioside-induced differentiation-associated-protein Gdap10 0.00015915 -2.04821NM_001081175 // Itpkb // inositol 1,4,5-trisphosphate 3-kinase B // 1 H5|1 84.27 cM // Itpkb 4.96E-06 -2.0484NM_008480 // Lama1 // laminin, alpha 1 // 17 E1.1|17 38.8 cM // 16772 /// ENSMUST000000 Lama1 0.00204748 -2.04967

--- 0.00266243 -2.05087NM_001113326 // Msr1 // macrophage scavenger receptor 1 // 8 A4|8 23.89 cM // 20288 /// Msr1 1.16E-05 -2.05358NM_009744 // Bcl6 // B cell leukemia/lymphoma 6 // 16 B1|16 15.26 cM // 12053 /// ENSMU Bcl6 2.08E-06 -2.05522NM_028132 // Pgm2 // phosphoglucomutase 2 // 4 C6|4 45.71 cM // 72157 /// ENSMUST000000 Pgm2 2.25E-05 -2.06347NM_201518 // Flrt2 // fibronectin leucine rich transmembrane protein 2 // 12 E|12 // 39 Flrt2 2.91E-05 -2.06362NR_040335 // D330050G23Rik // RIKEN cDNA D330050G23 gene // 2|2 // 320975 /// ENSMUST00 D330050G23Ri 0.000382936 -2.06404NM_008826 // Pfkl // phosphofructokinase, liver, B-type // 10 C1|10 39.72 cM // 18641 / Pfkl 6.93E-06 -2.06639NM_175175 // Plekhf2 // pleckstrin homology domain containing, family F (with FYVE doma Plekhf2 9.41E-06 -2.06807NM_026968 // Manbal // mannosidase, beta A, lysosomal-like // 2 H1|2 // 69161 /// ENSMU Manbal 2.77E-05 -2.0698ENSMUST00000101800 // Msrb1 // methionine sulfoxide reductase B1 // 17 A3.3|17 12.53 cM Msrb1 0.000746314 -2.07036NM_011016 // Orm2 // orosomucoid 2 // 4 C1|4 33.96 cM // 18406 /// ENSMUST00000075341 / Orm2 0.00345026 -2.07058--- 1.67E-05 -2.07229NM_207636 // Fndc3a // fibronectin type III domain containing 3A // 14 D2|14 37.62 cM / Fndc3a 3.78E-05 -2.07419NM_144522 // Tbc1d10b // TBC1 domain family, member 10b // 7|7 F4 // 68449 /// ENSMUST0 Tbc1d10b 0.000101801 -2.07449NM_001142809 // Slc6a8 // solute carrier family 6 (neurotransmitter transporter, creati Slc6a8 6.38E-08 -2.07514NM_009447 // Tuba4a // tubulin, alpha 4A // 1|1 C3 // 22145 /// ENSMUST00000079464 // T Tuba4a 6.92E-05 -2.07633NM_001145858 // Sh3bp2 // SH3-domain binding protein 2 // 5 B2|5 // 24055 /// NM_001145 Sh3bp2 6.01E-06 -2.07641--- 0.00100118 -2.07684NM_177607 // 4933430I17Rik // RIKEN cDNA 4933430I17 gene // 4 B3|4 // 214106 /// ENSMUS 4933430I17Rik 0.00185415 -2.07808NM_007793 // Cstb // cystatin B // 10 C1|10 39.72 cM // 13014 /// ENSMUST00000005185 // Cstb 0.000156285 -2.07975--- 0.000499137 -2.08044NM_010907 // Nfkbia // nuclear factor of kappa light polypeptide gene enhancer in B cel Nfkbia 0.000869502 -2.0823NM_001111279 // Wdfy1 // WD repeat and FYVE domain containing 1 // 1|1 C4 // 69368 /// Wdfy1 0.00363192 -2.08417NM_198642 // 5031414D18Rik // RIKEN cDNA 5031414D18 gene // 14 D3|14 // 271221 /// ENSM 5031414D18Rik 0.00094129 -2.08451ENSMUST00000135573 // Gm21399 // peroxiredoxin 1 pseudogene // 8|8 // 100862012 /// ENS Gm21399 1.32E-05 -2.08642ENSMUST00000101295 // 9930111J21Rik2 // RIKEN cDNA 9930111J21 gene 2 // 11 B1.2|11 // 2 9930111J21Rik 0.00356031 -2.08652NM_172428 // Ccdc134 // coiled-coil domain containing 134 // 15 E1|15 // 76457 /// XM_0 Ccdc134 0.000487045 -2.08729NM_001145935 // Zfp691 // zinc finger protein 691 // 4 D2.1|4 // 195522 /// NM_183140 / Zfp691 0.000149571 -2.08765NM_198007 // Ascc3 // activating signal cointegrator 1 complex subunit 3 // 10 B3|10 // Ascc3 0.000304546 -2.08949NM_001113569 // Stxbp1 // syntaxin binding protein 1 // 2 B|2 22.09 cM // 20910 /// NM_ Stxbp1 0.000135617 -2.08951NM_013566 // Itgb7 // integrin beta 7 // 15 F3|15 57.39 cM // 16421 /// ENSMUST00000001 Itgb7 0.000553297 -2.09165NM_008591 // Met // met proto-oncogene // 6 A2|6 7.83 cM // 17295 /// ENSMUST0000011544 Met 0.0023217 -2.09308NM_033601 // Bcl3 // B cell leukemia/lymphoma 3 // 7 A3|7 9.95 cM // 12051 /// ENSMUST0 Bcl3 0.000295204 -2.09505NM_019631 // Tmem45a // transmembrane protein 45a // 16 C1.1|16 // 56277 /// XM_0065223 Tmem45a 7.00E-06 -2.09581NM_011851 // Nt5e // 5 nucleotidase, ecto // 9|9 E3.2 // 23959 /// ENSMUST00000034992 / Nt5e 9.51E-06 -2.09696NR_038038 // Hk1os // hexokinase 1, opposite strand // 10 B4|10 // 70162 /// ENSMUST000 Hk1os 0.00248913 -2.10056NM_175529 // Leng9 // leukocyte receptor cluster (LRC) member 9 // 7 A1|7 // 243813 /// Leng9 0.00187146 -2.10084--- 0.00373139 -2.10306NM_013605 // Muc1 // mucin 1, transmembrane // 3 F1|3 39.02 cM // 17829 /// ENSMUST0000 Muc1 0.00269169 -2.1039NM_013712 // Itgb1bp2 // integrin beta 1 binding protein 2 // X|X D // 26549 /// ENSMUS Itgb1bp2 0.00151829 -2.10402NM_153422 // Pde5a // phosphodiesterase 5A, cGMP-specific // 3 G1|3 // 242202 /// XM_00 Pde5a 0.00180104 -2.10507ENSMUST00000080062 // Gm17541 // predicted gene, 17541 // --- // --- Gm17541 0.000333621 -2.10542NM_175523 // Ppm1k // protein phosphatase 1K (PP2C domain containing) // 6 B3|6 // 2433 Ppm1k 0.00130113 -2.10762--- 0.00417487 -2.10891ENSMUST00000152813 // Spata5l1 // spermatogenesis associated 5-like 1 // --- // --- /// Spata5l1 0.00217273 -2.10923NM_025427 // Rgcc // regulator of cell cycle // 14 D3|14 // 66214 /// XM_006519373 // R Rgcc 0.00184856 -2.10953ENSMUST00000092990 // Agpat9 // 1-acylglycerol-3-phosphate O-acyltransferase 9 // 5 E4| Agpat9 0.00116135 -2.11094--- 0.00168847 -2.11138NM_146893 // Olfr1216 // olfactory receptor 1216 // 2 E1|2 // 258895 /// ENSMUST0000009 Olfr1216 0.00116615 -2.11186NM_001114679 // 9930111J21Rik1 // RIKEN cDNA 9930111J21 gene 1 // 11 B1.2|11 // 667214 9930111J21Rik 0.000547307 -2.11421NM_001024474 // Diras2 // DIRAS family, GTP-binding RAS-like 2 // 13 A5|13 // 68203 /// Diras2 0.00126303 -2.11447NM_130864 // Acaa1a // acetyl-Coenzyme A acyltransferase 1A // 9 F4|9 71.33 cM // 11386 Acaa1a 0.00234895 -2.11497NM_133501 // Ntng2 // netrin G2 // 2 B|2 19.57 cM // 171171 /// ENSMUST00000048455 // N Ntng2 0.000910265 -2.11714NM_020042 // Mocs1 // molybdenum cofactor synthesis 1 // 17 C|17 // 56738 /// NM_028464 Mocs1 0.000533857 -2.11881NM_016846 // Rgl1 // ral guanine nucleotide dissociation stimulator,-like 1 // 1|1 G2 / Rgl1 0.000312751 -2.12013NM_029338 // Rsph9 // radial spoke head 9 homolog (Chlamydomonas) // 17|17 C // 75564 / Rsph9 0.00367718 -2.12095ENSMUST00000100700 // Gm10382 // predicted gene 10382 // --- // --- /// AK132914 // Gm1 Gm10382 0.00102916 -2.1233--- 0.000379934 -2.12619XM_006530180 // Msi1 // musashi RNA-binding protein 1 // 5 E3-F|5 // 17690 /// ENSMUST0 Msi1 0.00296668 -2.12641--- 0.00307879 -2.12813NM_173386 // Mb21d1 // Mab-21 domain containing 1 // 9 E1|9 // 214763 /// ENSMUST000000 Mb21d1 0.00367549 -2.12917ENSMUST00000160445 // Gm16549 // predicted gene 16549 // --- // --- /// AK007062 // Fnd Gm16549 0.000443703 -2.13071NM_019811 // Acss2 // acyl-CoA synthetase short-chain family member 2 // 2|2 H2 // 6052 Acss2 1.78E-06 -2.13268ENSMUST00000094754 // Rpl7a-ps8 // ribosomal protein L7A, pseudogene 8 // --- // --- Rpl7a-ps8 0.00345387 -2.13327NM_013491 // Clcn1 // chloride channel 1 // 6 B2.1|6 20.57 cM // 12723 /// ENSMUST00000 Clcn1 0.00376894 -2.14275NM_010870 // Naip5 // NLR family, apoptosis inhibitory protein 5 // 13 D1|13 53.05 cM / Naip5 2.25E-05 -2.145ENSMUST00000071792 // 1110038F14Rik // RIKEN cDNA 1110038F14 gene // 15|15 E1 // 117171 1110038F14Rik 0.000106131 -2.14511NM_023247 // Ndufaf3 // NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, assembly fa Ndufaf3 0.000161913 -2.14513NM_031406 // Slc12a9 // solute carrier family 12 (potassium/chloride transporters), mem Slc12a9 0.00017598 -2.14522NM_001252550 // BC017643 // cDNA sequence BC017643 // 11 E2|11 // 217370 /// NM_0012547 BC017643 1.23E-06 -2.14536NM_020497 // Zfp276 // zinc finger protein (C2H2 type) 276 // 8 E1|8 72.09 cM // 57247 Zfp276 0.000340053 -2.14634ENSMUST00000106854 // Trim34a // tripartite motif-containing 34A // 7|7 F1 // 94094 Trim34a 0.000965647 -2.14696NM_153805 // Pkn3 // protein kinase N3 // 2 B|2 // 263803 /// XM_006498052 // Pkn3 // p Pkn3 5.78E-05 -2.14825XM_006542015 // LOC102635000 // uncharacterized LOC102635000 // --- // 102635000 /// XM LOC102635000 0.00330601 -2.15012NM_008869 // Pla2g4a // phospholipase A2, group IVA (cytosolic, calcium-dependent) // 1 Pla2g4a 0.00238013 -2.15408NM_021355 // Fmod // fibromodulin // 1 E4|1 58.09 cM // 14264 /// ENSMUST00000048183 // Fmod 0.00156579 -2.1545NM_199322 // Dot1l // DOT1-like, histone H3 methyltransferase (S. cerevisiae) // 10 C1| Dot1l 3.79E-05 -2.15461NM_027450 // Glipr2 // GLI pathogenesis-related 2 // 4 B1|4 // 384009 /// ENSMUST000000 Glipr2 0.000835073 -2.15501NM_028451 // Larp1 // La ribonucleoprotein domain family, member 1 // 11|11 B2 // 73158 Larp1 0.000112722 -2.15504NM_023168 // Grina // glutamate receptor, ionotropic, N-methyl D-aspartate-associated p Grina 2.13E-06 -2.15531NM_001177843 // Frmd4a // FERM domain containing 4A // 2 A1|2 // 209630 /// NM_172475 / Frmd4a 6.38E-06 -2.15536NM_027334 // Mettl7a1 // methyltransferase like 7A1 // 15|15 F3 // 70152 /// XM_0065213 Mettl7a1 0.000203274 -2.15623NM_175013 // Pgm5 // phosphoglucomutase 5 // 19 B|19 // 226041 /// ENSMUST00000047666 / Pgm5 0.000154963 -2.15645NM_019932 // Pf4 // platelet factor 4 // 5 E1|5 // 56744 /// ENSMUST00000031320 // Pf4 Pf4 0.00122957 -2.15697ENSMUST00000105015 // Gm14347 // predicted gene 14347 // X A1.1|X // 627264 Gm14347 0.00366025 -2.15796ENSMUST00000157928 // Gm22101 // predicted gene, 22101 // --- // --- Gm22101 0.00149944 -2.15933NM_153583 // Atg4d // autophagy related 4D, cysteine peptidase // 9 A3|9 // 235040 /// Atg4d 0.000645001 -2.16203NM_007413 // Adora2b // adenosine A2b receptor // 11 B2|11 // 11541 /// ENSMUST00000018 Adora2b 0.00369613 -2.16409ENSMUST00000034522 // Clmp // CXADR-like membrane protein // 9 A5.1|9 // 71566 /// NM_1 Clmp 2.39E-11 -2.16549NM_001290667 // Chac2 // ChaC, cation transport regulator 2 // 11 A4|11 // 68044 /// NM Chac2 0.00245236 -2.1655--- 0.00152773 -2.16699NM_025286 // Slc31a2 // solute carrier family 31, member 2 // 4 B3|4 // 20530 /// ENSMU Slc31a2 0.000125318 -2.16726AK136930 // Gm4583 // predicted gene 4583 // 14 D1|14 // 100043676 Gm4583 0.00486052 -2.17333NM_011400 // Slc2a1 // solute carrier family 2 (facilitated glucose transporter), membe Slc2a1 8.00E-06 -2.17518--- 0.00365395 -2.17674

NM_033622 // Tnfsf13b // tumor necrosis factor (ligand) superfamily, member 13b // 8 A1 Tnfsf13b 0.000131607 -2.18635NM_013790 // Abcc5 // ATP-binding cassette, sub-family C (CFTR/MRP), member 5 // 16 A3| Abcc5 1.27E-05 -2.18771NM_001080926 // Lrp8 // low density lipoprotein receptor-related protein 8, apolipoprot Lrp8 2.31E-06 -2.18776NM_001289704 // Cflar // CASP8 and FADD-like apoptosis regulator // 1 C1.3|1 29.16 cM / Cflar 0.00365715 -2.18811NM_011174 // Prh1 // proline rich protein HaeIII subfamily 1 // 6 G1|6 64.03 cM // 1913 Prh1 0.000112794 -2.18921NM_009450 // Tubb2a // tubulin, beta 2A class IIA // 13 A3.3|13 14.03 cM // 22151 /// E Tubb2a 9.49E-06 -2.19402NM_009410 // Top3a // topoisomerase (DNA) III alpha // 11 B2|11 // 21975 /// ENSMUST000 Top3a 0.000596338 -2.1945NM_026438 // Ppa1 // pyrophosphatase (inorganic) 1 // 10 B4|10 32.25 cM // 67895 /// EN Ppa1 5.47E-06 -2.1947NM_001168684 // Tmcc3 // transmembrane and coiled coil domains 3 // 10 C2|10 // 319880 Tmcc3 0.00107634 -2.19602NM_011186 // Psmb5 // proteasome (prosome, macropain) subunit, beta type 5 // 14 C2-D1| Psmb5 3.23E-06 -2.19681NM_010172 // F7 // coagulation factor VII // 8 A1.1|8 5.73 cM // 14068 /// ENSMUST00000 F7 1.87E-06 -2.19724NM_007909 // Efna2 // ephrin A2 // 10 C1|10 39.72 cM // 13637 /// ENSMUST00000003154 // Efna2 0.00226483 -2.19935NR_073569 // Klrb1-ps1 // killer cell lectin-like receptor subfamily B member 1, pseudo Klrb1-ps1 0.0050933 -2.20314ENSMUST00000067924 // Lrrc8c // leucine rich repeat containing 8 family, member C // 5 Lrrc8c 7.37E-05 -2.20326NM_001037762 // Zdhhc12 // zinc finger, DHHC domain containing 12 // 2 B|2 // 66220 /// Zdhhc12 0.000118297 -2.20356NM_007808 // Cycs // cytochrome c, somatic // 6 B2.3|6 24.32 cM // 13063 /// ENSMUST000 Cycs 0.000129559 -2.20416NM_178796 // A530064D06Rik // RIKEN cDNA A530064D06 gene // 17 C|17 // 328830 /// ENSMU A530064D06Rik 4.61E-05 -2.20715ENSMUST00000145961 // Gm12764 // predicted gene 12764 // --- // --- Gm12764 0.000876045 -2.20885NM_009393 // Tnnc1 // troponin C, cardiac/slow skeletal // 14 B|14 19.09 cM // 21924 // Tnnc1 0.00172835 -2.21409--- 2.47E-06 -2.21453NM_177876 // Vps37b // vacuolar protein sorting 37B (yeast) // 5 F|5 // 330192 /// ENSM Vps37b 0.00137714 -2.21571NM_183426 // Sbno2 // strawberry notch homolog 2 (Drosophila) // 10 C1|10 // 216161 /// Sbno2 5.00E-07 -2.21628--- 0.000560039 -2.21812NM_023044 // Slc15a3 // solute carrier family 15, member 3 // 19|19 B // 65221 /// ENSM Slc15a3 2.12E-05 -2.22241NM_172733 // Dera // 2-deoxyribose-5-phosphate aldolase homolog (C. elegans) // 6 G1|6 Dera 3.10E-06 -2.22482--- 0.000401391 -2.2271ENSMUST00000180468 // Gm26510 // predicted gene, 26510 // --- // --- /// XR_397622 // L Gm26510 0.00113077 -2.22719NM_007802 // Ctsk // cathepsin K // 3 F2.1|3 40.74 cM // 13038 /// ENSMUST00000015664 / Ctsk 0.0011834 -2.23075NR_045687 // Gm9895 // predicted gene 9895 // 19 C1|19 // 100503337 Gm9895 0.000386221 -2.23188NM_008851 // Pitpnm1 // phosphatidylinositol transfer protein, membrane-associated 1 // Pitpnm1 3.78E-06 -2.23632--- 0.000348463 -2.23985NM_153074 // Lrrc25 // leucine rich repeat containing 25 // 8 B3.3|8 // 211228 /// ENSM Lrrc25 0.000384073 -2.24163--- 0.000150386 -2.24358NM_009621 // Adamts1 // a disintegrin-like and metallopeptidase (reprolysin type) with Adamts1 0.00284844 -2.24463NM_026073 // Ift22 // intraflagellar transport 22 // 5|5 G1 // 67286 /// ENSMUST0000000 Ift22 2.79E-05 -2.24949NM_013913 // Angptl3 // angiopoietin-like 3 // 4 C6|4 45.6 cM // 30924 /// ENSMUST00000 Angptl3 0.000100375 -2.25096NM_028035 // Snx10 // sorting nexin 10 // 6 B3|6 // 71982 /// NM_001127348 // Snx10 // Snx10 1.86E-05 -2.25102NM_178892 // Tiparp // TCDD-inducible poly(ADP-ribose) polymerase // 3 E1|3 // 99929 // Tiparp 9.00E-05 -2.25291ENSMUST00000027256 // Gm6238 // predicted pseudogene 6238 // X D|X // 621542 /// ENSMUS Gm6238 0.0012727 -2.25544NM_027490 // Dcp2 // DCP2 decapping enzyme homolog (S. cerevisiae) // 18 B3|18 // 70640 Dcp2 0.000194515 -2.2562NM_001284300 // Aifm2 // apoptosis-inducing factor, mitochondrion-associated 2 // 10 B4 Aifm2 4.17E-05 -2.25666NR_045747 // Gm10872 // predicted gene 10872 // --- // 100038659 Gm10872 0.00243666 -2.25849--- 0.00040573 -2.25855NM_172652 // Kansl3 // KAT8 regulatory NSL complex subunit 3 // 1 B|1 // 226976 /// XM_ Kansl3 9.46E-06 -2.2597NM_001159417 // Irf9 // interferon regulatory factor 9 // 14 C3|14 28.19 cM // 16391 // Irf9 0.000153428 -2.26181NR_110420 // Ptgs2os2 // prostaglandin-endoperoxide synthase 2, opposite strand 2 // 1 Ptgs2os2 0.00315984 -2.26394NM_172477 // Dennd2a // DENN/MADD domain containing 2A // 6 B1|6 // 209773 /// XM_00650 Dennd2a 0.00359475 -2.26503NM_001081684 // Zbtb21 // zinc finger and BTB domain containing 21 // 16|16 C3-4 // 114 Zbtb21 9.24E-05 -2.26536NM_023422 // Hist1h2bc // histone cluster 1, H2bc // 13 A3.1|13 // 68024 /// ENSMUST000 Hist1h2bc 3.09E-05 -2.26698NM_001288586 // Mdm2 // transformed mouse 3T3 cell double minute 2 // 10 C1-C3|10 66.32 Mdm2 4.67E-06 -2.26744NM_009546 // Trim25 // tripartite motif-containing 25 // 11 C|11 // 217069 /// ENSMUST0 Trim25 5.06E-05 -2.26929ENSMUST00000134427 // Gm11613 // predicted gene 11613 // --- // --- /// AK052674 // LOC Gm11613 2.97E-05 -2.27133NM_145478 // Pim3 // proviral integration site 3 // 15 E3|15 // 223775 /// ENSMUST00000 Pim3 0.00132224 -2.27519NM_027314 // March5 // membrane-associated ring finger (C3HC4) 5 // 19 C2|19 // 69104 / Mar-05 0.000261791 -2.27614NR_045304 // 1700030N03Rik // RIKEN cDNA 1700030N03 gene // --- // 70011 1700030N03Rik 0.00276018 -2.27799NM_172939 // Sowahc // sosondowah ankyrin repeat domain family member C // 10 B4|10 // Sowahc 5.02E-07 -2.27954NM_144905 // 6330416G13Rik // RIKEN cDNA 6330416G13 gene // 4 C1|4 // 230279 /// XM_006 6330416G13Rik 8.55E-05 -2.28047NM_019467 // Aif1 // allograft inflammatory factor 1 // 17 B1|17 18.59 cM // 11629 /// Aif1 1.76E-05 -2.2811NM_175326 // D330045A20Rik // RIKEN cDNA D330045A20 gene // X F1|X // 102871 /// ENSMUS D330045A20Rik 0.00012973 -2.28168NM_019587 // Plxnb3 // plexin B3 // X A7.3|X // 140571 /// ENSMUST00000002079 // Plxnb3 Plxnb3 0.000268931 -2.2832NM_021788 // Sap30 // sin3 associated polypeptide // 8 B2|8 29.85 cM // 60406 /// ENSMU Sap30 2.12E-06 -2.2835NM_026565 // Apool // apolipoprotein O-like // X|X E2 // 68117 /// XM_006528405 // Apoo Apool 5.73E-06 -2.28659NM_001253860 // Scn5a // sodium channel, voltage-gated, type V, alpha // 9 F3-F4|9 71.3 Scn5a 0.000101821 -2.29636NM_178732 // Zfp324 // zinc finger protein 324 // 7 A1|7 // 243834 /// ENSMUST000000387 Zfp324 0.00225839 -2.29892NM_145836 // Irf2bpl // interferon regulatory factor 2 binding protein-like // 12 D2|12 Irf2bpl 0.00263065 -2.30053XM_006505152 // Zfp800 // zinc finger protein 800 // 6 A3.2|6 // 627049 /// ENSMUST0000 Zfp800 5.69E-05 -2.30382NM_133819 // Ppp1r15b // protein phosphatase 1, regulatory (inhibitor) subunit 15b // 1 Ppp1r15b 4.27E-06 -2.3042ENSMUST00000171158 // Sdc1 // syndecan 1 // 12 A1.1|12 3.94 cM // 20969 /// ENSMUST0000 Sdc1 1.97E-05 -2.30979NM_172450 // 4930539E08Rik // RIKEN cDNA 4930539E08 gene // 17 A3.3|17 // 207819 /// EN 4930539E08Rik 0.00265388 -2.31179XM_006511595 // A730067D02Rik // RIKEN cDNA A730067D02 gene // 9 C|9 // 330963 /// XM_0 A730067D02Rik 0.00100221 -2.31798NM_001190461 // Hilpda // hypoxia inducible lipid droplet associated // 6 A3.3|6 // 695 Hilpda 3.37E-05 -2.32087--- 4.50E-05 -2.32118NM_153507 // Cpne2 // copine II // 8 C5|8 // 234577 /// ENSMUST00000048653 // Cpne2 // Cpne2 9.76E-06 -2.32527--- 0.000957816 -2.32629NM_016808 // Usp2 // ubiquitin specific peptidase 2 // 9|9 B // 53376 /// NM_198092 // Usp2 1.42E-05 -2.32737NM_001290504 // Mid1 // midline 1 // X and Y|X 79.19 cM // 17318 /// NM_001290505 // Mi Mid1 7.98E-05 -2.32755NM_031380 // Fstl3 // follistatin-like 3 // 10 C1|10 // 83554 /// ENSMUST00000020575 // Fstl3 4.24E-05 -2.32891NM_001080769 // Uhrf1bp1 // UHRF1 (ICBP90) binding protein 1 // 17 A3.3|17 // 224648 // Uhrf1bp1 0.000564468 -2.32991NM_008990 // Pvrl2 // poliovirus receptor-related 2 // 7 A3|7 9.94 cM // 19294 /// ENSM Pvrl2 0.000100864 -2.33091--- 6.07E-06 -2.33108--- 6.07E-06 -2.33108NM_001284397 // Gngt2 // guanine nucleotide binding protein (G protein), gamma transduc Gngt2 0.000380636 -2.33131NM_172393 // Aim1 // absent in melanoma 1 // 10 B2|10 23.14 cM // 11630 /// ENSMUST0000 Aim1 7.56E-06 -2.3316NM_001256515 // AI837181 // expressed sequence AI837181 // 19 A|19 // 107242 /// NM_134 AI837181 9.76E-05 -2.33338NM_145122 // Pex16 // peroxisomal biogenesis factor 16 // 2 E1|2 // 18633 /// ENSMUST00 Pex16 2.88E-05 -2.33617--- 0.00227385 -2.33844XM_006530302 // Trafd1 // TRAF type zinc finger domain containing 1 // 5 F|5 // 231712 Trafd1 7.14E-08 -2.33876NR_045324 // Gm19705 // predicted gene, 19705 // 1 E4-F|1 59.94 cM // 100503460 /// NR_ Gm19705 0.0027215 -2.3415NM_145619 // Parp3 // poly (ADP-ribose) polymerase family, member 3 // 9 F1|9 // 235587 Parp3 1.12E-05 -2.34674NM_023526 // Nkiras1 // NFKB inhibitor interacting Ras-like protein 1 // 14|14 A3 // 69 Nkiras1 0.000823428 -2.35021NM_013885 // Clic4 // chloride intracellular channel 4 (mitochondrial) // 4 D3|4 // 298 Clic4 0.000432639 -2.35524NM_009448 // Tuba1c // tubulin, alpha 1C // 15 F1|15 // 22146 /// ENSMUST00000058914 // Tuba1c 7.31E-05 -2.35604ENSMUST00000139214 // 4930430E12Rik // RIKEN cDNA 4930430E12 gene // --- // --- /// ENS 4930430E12Rik 3.78E-06 -2.3561NM_009716 // Atf4 // activating transcription factor 4 // 15 E1|15 37.85 cM // 11911 // Atf4 4.66E-06 -2.35746NM_001110824 // Foxp4 // forkhead box P4 // 17 C|17 // 74123 /// NM_001110825 // Foxp4 Foxp4 0.00192242 -2.36225

--- 0.00322059 -2.36295NM_001122680 // Pvrl4 // poliovirus receptor-related 4 // 1 H2|1 // 71740 /// NM_027893 Pvrl4 0.000167128 -2.36392ENSMUST00000032429 // Med21 // mediator complex subunit 21 // 6 G3|6 77.7 cM // 108098 Med21 0.000133525 -2.36463NM_001113374 // Mocs2 // molybdenum cofactor synthesis 2 // 13 D2.2|13 // 17434 /// NM_ Mocs2 7.01E-05 -2.36557NM_011109 // Pla2g2d // phospholipase A2, group IID // 4 D3|4 70.57 cM // 18782 /// ENS Pla2g2d 0.00447822 -2.36783NM_173027 // Ip6k3 // inositol hexaphosphate kinase 3 // 17 A3.3|17 // 271424 /// ENSMU Ip6k3 0.00439446 -2.3707NM_001039530 // Parp14 // poly (ADP-ribose) polymerase family, member 14 // 16 B3|16 // Parp14 0.00127358 -2.37282XM_006530858 // Inpp4b // inositol polyphosphate-4-phosphatase, type II // 8 C2|8 39.02 Inpp4b 0.00110877 -2.37819NM_008670 // Naip1 // NLR family, apoptosis inhibitory protein 1 // 13 D1-D3|13 53.18 c Naip1 2.03E-06 -2.38165ENSMUST00000068569 // Bcl2a1b // B cell leukemia/lymphoma 2 related protein A1b // 9 E3 Bcl2a1b 0.000623851 -2.38324NM_013654 // Ccl7 // chemokine (C-C motif) ligand 7 // 11 C|11 49.83 cM // 20306 /// EN Ccl7 0.00150352 -2.38744NM_010871 // Naip6 // NLR family, apoptosis inhibitory protein 6 // 13 D1|13 53.09 cM / Naip6 0.000525516 -2.3904NM_178728 // Napepld // N-acyl phosphatidylethanolamine phospholipase D // 5 A3|5 // 24 Napepld 0.000247041 -2.39101NM_023655 // Trim29 // tripartite motif-containing 29 // 9 A5.1|9 // 72169 /// ENSMUST0 Trim29 0.00326675 -2.39199NM_001142642 // Fbrsl1 // fibrosin-like 1 // 5 F|5 // 381668 /// NM_028596 // Fbrsl1 // Fbrsl1 6.69E-05 -2.39265NM_144559 // Fcgr4 // Fc receptor, IgG, low affinity IV // 1 H3|1 78.53 cM // 246256 // Fcgr4 1.64E-06 -2.39319NM_001164071 // Tank // TRAF family member-associated Nf-kappa B activator // 2 C1.3|2 Tank 3.66E-05 -2.39378NR_040374 // A230028O05Rik // RIKEN cDNA A230028O05 gene // 16 B1|16 // 319487 /// ENSM A230028O05Rik 0.000109621 -2.39503ENSMUST00000136542 // Gm11772 // predicted gene 11772 // --- // --- Gm11772 0.0045589 -2.39584ENSMUST00000160432 // Gm16231 // predicted gene 16231 // --- // --- Gm16231 0.000313293 -2.39589NM_001141981 // Rbm43 // RNA binding motif protein 43 // 2|2 C1 // 71684 /// NM_0011419 Rbm43 1.34E-06 -2.40032NM_025730 // Lrrk2 // leucine-rich repeat kinase 2 // 15|15 F1 // 66725 /// XM_00652127 Lrrk2 6.74E-05 -2.40049NM_007801 // Ctsh // cathepsin H // 9 E3.1|9 47.4 cM // 13036 /// ENSMUST00000034915 // Ctsh 1.80E-05 -2.4011NM_010628 // Kif9 // kinesin family member 9 // 9 F2|9 // 16578 /// XM_006511941 // Kif Kif9 0.000536368 -2.40227NM_029077 // Trim14 // tripartite motif-containing 14 // 4|4 B2 // 74735 /// ENSMUST000 Trim14 5.92E-06 -2.41186NM_001048207 // Gypc // glycophorin C // 18 B1|18 18.05 cM // 71683 /// ENSMUST00000174 Gypc 8.15E-05 -2.41439NM_001033136 // Rmdn3 // regulator of microtubule dynamics 3 // 2 E5|2 // 67809 /// ENS Rmdn3 3.90E-05 -2.41515NM_001038998 // Ccdc23 // coiled-coil domain containing 23 // 4 D2.1|4 // 69216 /// ENS Ccdc23 0.000170594 -2.41629ENSMUST00000101477 // Peli1 // pellino 1 // 11 A3.2|11 13.81 cM // 67245 /// AF302503 / Peli1 4.91E-05 -2.41807NM_001163590 // Stx11 // syntaxin 11 // 10 A1|10 // 74732 /// NM_029075 // Stx11 // syn Stx11 0.00121746 -2.42205NM_172722 // Naa25 // N(alpha)-acetyltransferase 25, NatB auxiliary subunit // 5 F|5 // Naa25 6.32E-07 -2.42505NM_016873 // Wisp2 // WNT1 inducible signaling pathway protein 2 // 2 H3|2 // 22403 /// Wisp2 0.00245095 -2.42598NM_001048060 // Idnk // idnK gluconokinase homolog (E. coli) // 13 B1|13 // 75731 /// N Idnk 8.60E-05 -2.42637ENSMUST00000164181 // Gm8894 // myosin light polypeptide 6 alkali smooth muscle and non Gm8894 0.00337687 -2.42934XR_140681 // 4930455G09Rik // RIKEN cDNA 4930455G09 gene // 4|4 // 78917 /// ENSMUST000 4930455G09Rik 0.000102308 -2.4294--- 0.00074689 -2.43102NM_007498 // Atf3 // activating transcription factor 3 // 1 H6|1 96.28 cM // 11910 /// Atf3 1.59E-07 -2.43244NM_001025427 // Hmga1 // high mobility group AT-hook 1 // 17 A3.3|17 14.5 cM // 15361 / Hmga1 6.47E-06 -2.43484NM_008353 // Il12rb1 // interleukin 12 receptor, beta 1 // 8 B3.3|8 34.21 cM // 16161 / Il12rb1 9.30E-05 -2.43677NM_001160181 // Tor1aip2 // torsin A interacting protein 2 // 1 G3|1 // 240832 /// NM_0 Tor1aip2 3.47E-05 -2.44072NM_019564 // Htra1 // HtrA serine peptidase 1 // 7 F3|7 // 56213 /// ENSMUST00000006367 Htra1 0.000142207 -2.44143NM_172734 // Stk38l // serine/threonine kinase 38 like // 6 G3|6 // 232533 /// XM_00650 Stk38l 0.000277625 -2.44313NM_010050 // Dio2 // deiodinase, iodothyronine, type II // 12 D3|12 // 13371 /// ENSMUS Dio2 0.000421833 -2.45278NM_172488 // Lacc1 // laccase (multicopper oxidoreductase) domain containing 1 // 14 D3 Lacc1 0.00333518 -2.45313NM_008871 // Serpine1 // serine (or cysteine) peptidase inhibitor, clade E, member 1 // Serpine1 0.000167515 -2.45348NM_011030 // P4ha1 // procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydr P4ha1 5.18E-06 -2.46161NM_173052 // Serpinb1b // serine (or cysteine) peptidase inhibitor, clade B, member 1b Serpinb1b 0.00276314 -2.46649ENSMUST00000031670 // Gng11 // guanine nucleotide binding protein (G protein), gamma 11 Gng11 0.000347535 -2.46879NM_001165919 // 1700123I01Rik // RIKEN cDNA 1700123I01 gene // 19 A|19 // 622554 /// XM 1700123I01Rik 6.23E-05 -2.47392ENSMUST00000033900 // Rab20 // RAB20, member RAS oncogene family // 8 A1.1|8 5.73 cM // Rab20 5.53E-05 -2.4746XM_006543313 // 1700066C05Rik // RIKEN cDNA 1700066C05 gene // 16 C3.3|16 // 78654 /// 1700066C05Rik 0.00472468 -2.48008NM_011426 // Siglec1 // sialic acid binding Ig-like lectin 1, sialoadhesin // 2 F-H1|2 Siglec1 2.68E-05 -2.48428--- 0.00491607 -2.48575ENSMUST00000111314 // Adamts4 // a disintegrin-like and metallopeptidase (reprolysin ty Adamts4 0.00504282 -2.48956NM_001146348 // Eng // endoglin // 2 B|2 22.09 cM // 13805 /// NM_001146350 // Eng // e Eng 8.79E-06 -2.49369ENSMUST00000161540 // Gm17017 // predicted gene 17017 // --- // --- Gm17017 4.18E-05 -2.49573--- 3.06E-05 -2.4961NM_133661 // Slc6a12 // solute carrier family 6 (neurotransmitter transporter, betaine/ Slc6a12 0.000328268 -2.49863NM_010734 // Lst1 // leukocyte specific transcript 1 // 17 B1|17 18.59 cM // 16988 /// Lst1 0.00118117 -2.5037NM_026929 // Chac1 // ChaC, cation transport regulator 1 // 2 E5|2 // 69065 /// ENSMUST Chac1 0.00347382 -2.50389NM_010548 // Il10 // interleukin 10 // 1 E4|1 56.89 cM // 16153 /// ENSMUST00000016673 Il10 0.00137487 -2.506NM_207244 // Cd200r4 // CD200 receptor 4 // 16 B4|16 // 239849 /// XM_006522128 // Cd20 Cd200r4 6.51E-07 -2.50708NM_027514 // Pvr // poliovirus receptor // 7 A3|7 9.95 cM // 52118 /// ENSMUST000000435 Pvr 0.000102952 -2.51035NM_172668 // Lrp4 // low density lipoprotein receptor-related protein 4 // 2 E1|2 50.63 Lrp4 0.000260267 -2.51338NM_001146308 // Dbnl // drebrin-like // 11 A1|11 3.87 cM // 13169 /// NM_001146309 // D Dbnl 6.01E-06 -2.51397NM_010757 // Mafk // v-maf musculoaponeurotic fibrosarcoma oncogene family, protein K ( Mafk 3.90E-06 -2.51404NM_031178 // Tlr9 // toll-like receptor 9 // 9 F1|9 // 81897 /// ENSMUST00000062241 // Tlr9 5.89E-05 -2.51771NM_011163 // Eif2ak2 // eukaryotic translation initiation factor 2-alpha kinase 2 // 17 Eif2ak2 0.000509736 -2.52296ENSMUST00000154924 // Pnpt1 // polyribonucleotide nucleotidyltransferase 1 // 11|11 A4 Pnpt1 3.28E-06 -2.52306AK079938 // BE692007 // expressed sequence BE692007 // 19|19 8.44 cM // 100504727 /// X BE692007 0.00358327 -2.52549NM_009642 // Agtrap // angiotensin II, type I receptor-associated protein // 4 E1|4 78. Agtrap 4.59E-06 -2.5258NM_001177730 // Nr1h3 // nuclear receptor subfamily 1, group H, member 3 // 2 E1|2 50.5 Nr1h3 6.78E-06 -2.53437--- 0.00532235 -2.53608ENSMUST00000174525 // H2-Q10 // histocompatibility 2, Q region locus 10 // 17 B1|17 18. H2-Q10 0.00114793 -2.54313NM_172697 // Prpf38a // PRP38 pre-mRNA processing factor 38 (yeast) domain containing A Prpf38a 1.90E-05 -2.5442NM_001167991 // Hook2 // hook homolog 2 (Drosophila) // 8 C3|8 // 170833 /// NM_133255 Hook2 0.000680921 -2.54643--- 0.000399475 -2.55054NM_053267 // Selm // selenoprotein M // 11 A1|11 // 114679 /// ENSMUST00000094469 // Se Selm 1.66E-05 -2.55707NM_145857 // Nod2 // nucleotide-binding oligomerization domain containing 2 // 8 C3|8 / Nod2 0.000137645 -2.55843NM_139128 // Coro6 // coronin 6 // 11 B5|11 // 216961 /// NM_139129 // Coro6 // coronin Coro6 0.000418072 -2.57213NM_007555 // Bmp5 // bone morphogenetic protein 5 // 9 D|9 42.34 cM // 12160 /// ENSMUS Bmp5 0.000459215 -2.57515ENSMUST00000025904 // Prdx5 // peroxiredoxin 5 // 19 A|19 5.08 cM // 54683 /// ENSMUST0 Prdx5 2.30E-06 -2.57932AK037717 // A130040M12Rik // RIKEN cDNA A130040M12 gene // 11 C|11 // 319269 A130040M12Ri 0.000857389 -2.58326NM_011756 // Zfp36 // zinc finger protein 36 // 7 A3|7 16.72 cM // 22695 /// ENSMUST000 Zfp36 4.46E-05 -2.58413ENSMUST00000181222 // Gm16754 // predicted gene, 16754 // 9|9 7.74 cM // 100503569 /// Gm16754 0.000866289 -2.58519NM_001159301 // Lgals9 // lectin, galactose binding, soluble 9 // 11 B5|11 // 16859 /// Lgals9 0.000197965 -2.58606NM_001159393 // Irf1 // interferon regulatory factor 1 // 11 B1.3|11 32.0 cM // 16362 / Irf1 0.00167596 -2.58738NR_040442 // AV051173 // expressed sequence AV051173 // 4|4 // 100502959 AV051173 8.27E-05 -2.58751NR_073559 // Stxbp3b // syntaxin-binding protein 3B // 19 A|19 // 619371 /// ENSMUST000 Stxbp3b 0.00518755 -2.592NM_001252459 // Cyfip2 // cytoplasmic FMR1 interacting protein 2 // 11|11 B1.2 // 76884 Cyfip2 2.03E-07 -2.59335NM_001110305 // Keap1 // kelch-like ECH-associated protein 1 // 9 A3|9 // 50868 /// NM_ Keap1 6.99E-05 -2.59816ENSMUST00000073080 // Cycs // cytochrome c, somatic // 6 B2.3|6 24.32 cM // 13063 Cycs 0.000156804 -2.60145NR_028589 // Gm14005 // predicted gene 14005 // 2 F1|2 // 100043424 /// NR_028590 // Gm Gm14005 0.00138646 -2.60181NR_045932 // Slfn5os // schlafen 5, opposite strand // 11 C|11 // 76392 /// ENSMUST0000 Slfn5os 4.02E-05 -2.60185XR_392965 // 1110002J07Rik // RIKEN cDNA 1110002J07 gene // 10|10 // 68488 /// ENSMUST0 1110002J07Rik 0.00334135 -2.60518

NM_207105 // H2-Ab1 // histocompatibility 2, class II antigen A, beta 1 // 17 B1|17 17. H2-Ab1 0.000117317 -2.60702NM_011504 // Stxbp3a // syntaxin binding protein 3A // 3 F3|3 // 20912 /// ENSMUST00000 Stxbp3a 2.82E-05 -2.61196NM_011189 // Psme1 // proteasome (prosome, macropain) activator subunit 1 (PA28 alpha) Psme1 3.33E-06 -2.61561ENSMUST00000181212 // 2310031A07Rik // RIKEN cDNA 2310031A07 gene // --- // --- /// AK0 2310031A07Rik 0.00309526 -2.62066XM_006533512 // Slc22a4 // solute carrier family 22 (organic cation transporter), membe Slc22a4 4.83E-06 -2.63049ENSMUST00000172796 // Gm20496 // predicted gene 20496 // --- // --- /// ENSMUST00000173 Gm20496 0.00340254 -2.63631NM_010637 // Klf4 // Kruppel-like factor 4 (gut) // 4 B3|4 29.76 cM // 16600 /// ENSMUS Klf4 0.000811499 -2.63856XM_006543523 // Gm7160 // predicted gene 7160 // 1 E2.1|1 // 635504 Gm7160 0.000459108 -2.63966XM_006544796 // Gm10499 // predicted gene 10499 // 17 B1|17 // 69717 /// ENSMUST0000017 Gm10499 0.000949221 -2.64043NM_007611 // Casp7 // caspase 7 // 19 D2|19 51.84 cM // 12369 /// ENSMUST00000026062 // Casp7 0.000606381 -2.64162NM_007523 // Bak1 // BCL2-antagonist/killer 1 // 17|17 B // 12018 /// ENSMUST0000002503 Bak1 2.41E-05 -2.6424NM_009890 // Ch25h // cholesterol 25-hydroxylase // 19 C1|19 // 12642 /// ENSMUST000000 Ch25h 0.00264177 -2.64594NM_001097980 // Gm16390 // predicted gene 16390 // X F3|X // 100040937 /// ENSMUST00000 Gm16390 0.00422242 -2.64628NM_174850 // Micall2 // MICAL-like 2 // 5 G2|5 // 231830 /// ENSMUST00000044642 // Mica Micall2 0.00146832 -2.64674NM_030743 // Rnf114 // ring finger protein 114 // 2 H3|2 // 81018 /// XM_006500439 // R Rnf114 1.16E-06 -2.64689NM_008416 // Junb // jun B proto-oncogene // 8 C2-D1|8 41.41 cM // 16477 /// ENSMUST000 Junb 4.18E-08 -2.65596NM_001033290 // Gpr55 // G protein-coupled receptor 55 // 1 C5|1 // 227326 /// XM_00652 Gpr55 1.74E-05 -2.66508ENSMUST00000109212 // Gm5431 // predicted gene 5431 // 11 B1.2|11 // 432555 Gm5431 0.000554103 -2.66563NM_001128605 // Psen2 // presenilin 2 // 1 H4|1 84.19 cM // 19165 /// NM_011183 // Psen Psen2 1.35E-05 -2.66847NM_001048177 // Jak2 // Janus kinase 2 // 19 C1|19 23.73 cM // 16452 /// NM_008413 // J Jak2 0.00206559 -2.67129NM_001126182 // Naip2 // NLR family, apoptosis inhibitory protein 2 // 13 D1|13 53.01 c Naip2 0.000257077 -2.67431NM_025821 // Carhsp1 // calcium regulated heat stable protein 1 // 16 A1|16 4.26 cM // Carhsp1 4.49E-05 -2.67486XM_006504642 // Gm15753 // predicted gene 15753 // 5 G2|5 // 624083 Gm15753 0.000626721 -2.6835--- 0.00305952 -2.69175--- 0.00305952 -2.69175NM_008748 // Dusp8 // dual specificity phosphatase 8 // 7 F5|7 87.59 cM // 18218 /// EN Dusp8 0.000971951 -2.69888NM_012044 // Pla2g2e // phospholipase A2, group IIE // 4 D3|4 // 26970 /// ENSMUST00000 Pla2g2e 9.90E-05 -2.70094NR_030490 // Mir709 // microRNA 709 // 8|8 // 735271 /// ENSMUST00000102190 // Mir709 / Mir709 0.000483095 -2.70321NM_026827 // Tmem219 // transmembrane protein 219 // 7|7 F4 // 68742 /// NM_028389 // T Tmem219 2.21E-05 -2.70515NM_001033310 // Cox18 // cytochrome c oxidase assembly protein 18 // 5 E1|5 // 231430 / Cox18 3.49E-06 -2.70979NM_133871 // Ifi44 // interferon-induced protein 44 // 3 H3|3 // 99899 /// ENSMUST00000 Ifi44 0.000188361 -2.71458ENSMUST00000173249 // Gm20412 // predicted gene 20412 // --- // --- Gm20412 1.38E-05 -2.7172ENSMUST00000031766 // Asns // asparagine synthetase // 6 A1|6 // 27053 /// NM_012055 // Asns 4.66E-07 -2.71837NR_045641 // F630111L10Rik // RIKEN cDNA F630111L10 gene // 3 D|3 // 320463 /// AK17084 F630111L10Rik 1.05E-05 -2.71976ENSMUST00000119109 // Etv3 // ets variant 3 // 3 F1|3 // 27049 /// NM_001083318 // Etv3 Etv3 1.16E-06 -2.72481ENSMUST00000157098 // Gm26278 // predicted gene, 26278 // --- // --- Gm26278 0.00113827 -2.72966NM_011785 // Akt3 // thymoma viral proto-oncogene 3 // 1|1 H4-H6 // 23797 /// XM_006496 Akt3 3.52E-06 -2.73105NM_173051 // Serpinb1c // serine (or cysteine) peptidase inhibitor, clade B, member 1c Serpinb1c 0.000144642 -2.74145NM_018825 // Sh2b2 // SH2B adaptor protein 2 // 5|5 G1 // 23921 /// XM_006504420 // Sh2 Sh2b2 7.17E-05 -2.74343NM_029084 // Slamf8 // SLAM family member 8 // 1|1 H2 // 74748 /// ENSMUST00000065679 / Slamf8 0.00035631 -2.74359NM_026115 // Hat1 // histone aminotransferase 1 // 2 C2|2 // 107435 /// ENSMUST00000028 Hat1 5.22E-06 -2.74458NM_021547 // Stard3 // START domain containing 3 // 11 D|11 // 59045 /// XM_006533897 / Stard3 7.84E-07 -2.74928NM_001009573 // Unc13d // unc-13 homolog D (C. elegans) // 11 E2|11 // 70450 /// ENSMUS Unc13d 5.82E-06 -2.75205NM_011957 // Creb3l1 // cAMP responsive element binding protein 3-like 1 // 2 E1|2 // 2 Creb3l1 0.000214894 -2.76329NM_013819 // H2-M3 // histocompatibility 2, M region locus 3 // 17 B1|17 19.16 cM // 14 H2-M3 6.23E-07 -2.7666XR_397421 // Gm19412 // predicted gene, 19412 // 17|17 17.98 cM // 100502849 Gm19412 1.44E-05 -2.76737NM_001130476 // Tpst1 // protein-tyrosine sulfotransferase 1 // 5|5 F-G1 // 22021 /// N Tpst1 0.000629664 -2.77363--- 3.32E-06 -2.78168ENSMUST00000104261 // Gm23127 // predicted gene, 23127 // --- // --- /// AK163470 // El Gm23127 0.000194416 -2.78272NM_013640 // Psmb10 // proteasome (prosome, macropain) subunit, beta type 10 // 8 D3|8 Psmb10 0.000211328 -2.79112NM_021272 // Fabp7 // fatty acid binding protein 7, brain // 10 B4|10 // 12140 /// ENSM Fabp7 5.76E-07 -2.79452NM_029219 // Rnf19b // ring finger protein 19B // 4|4 D2.3 // 75234 /// ENSMUST00000030 Rnf19b 1.98E-06 -2.79552NM_026840 // Pdgfrl // platelet-derived growth factor receptor-like // 8 A4|8 // 68797 Pdgfrl 1.64E-05 -2.79586ENSMUST00000160076 // Gm16213 // predicted gene 16213 // --- // --- Gm16213 0.00193404 -2.80082NM_001101467 // Cyp2a22 // cytochrome P450, family 2, subfamily a, polypeptide 22 // 7 Cyp2a22 0.00403914 -2.80326NM_001170853 // Mndal // myeloid nuclear differentiation antigen like // 1 H3|1 // 1000 Mndal 0.000649485 -2.80361NM_001167946 // Zfp821 // zinc finger protein 821 // 8 D3|8 // 75871 /// NM_001286391 / Zfp821 3.59E-05 -2.81239NM_001146318 // Cnp // 2,3-cyclic nucleotide 3 phosphodiesterase // 11 D|11 63.47 cM // Cnp 1.97E-05 -2.81779NM_001161847 // Sgk1 // serum/glucocorticoid regulated kinase 1 // 10 A3|10 // 20393 // Sgk1 7.62E-08 -2.81889NM_001029929 // Zmynd15 // zinc finger, MYND-type containing 15 // 11 B3|11 // 574428 / Zmynd15 6.04E-07 -2.82019NM_001081020 // Adamts6 // a disintegrin-like and metallopeptidase (reprolysin type) wi Adamts6 7.65E-05 -2.83431NM_016767 // Batf // basic leucine zipper transcription factor, ATF-like // 12 D2|12 // Batf 0.000315305 -2.84022NM_183201 // Slfn5 // schlafen 5 // 11 C|11 // 327978 /// XR_388481 // Slfn5 // schlafe Slfn5 4.57E-05 -2.84258NM_015811 // Rgs1 // regulator of G-protein signaling 1 // 1 F|1 62.56 cM // 50778 /// Rgs1 2.56E-05 -2.85173NM_008654 // Ppp1r15a // protein phosphatase 1, regulatory (inhibitor) subunit 15A // 7 Ppp1r15a 6.29E-06 -2.85307NM_001163573 // Scnm1 // sodium channel modifier 1 // 3 F2|3 40.74 cM // 69269 /// NM_0 Scnm1 2.05E-05 -2.85328NM_011066 // Per2 // period circadian clock 2 // 1|1 C5 // 18627 /// ENSMUST00000069620 Per2 1.66E-05 -2.87106NM_001162365 // Ptk2b // PTK2 protein tyrosine kinase 2 beta // 14 D1|14 34.36 cM // 19 Ptk2b 3.72E-07 -2.88217ENSMUST00000032815 // Nfkbib // nuclear factor of kappa light polypeptide gene enhancer Nfkbib 9.28E-05 -2.88393ENSMUST00000049281 // Fam53c // family with sequence similarity 53, member C // 18 B1|1 Fam53c 8.45E-05 -2.89129NM_026942 // Stoml1 // stomatin-like 1 // 9 B|9 // 69106 /// NR_028146 // Stoml1 // sto Stoml1 0.00028948 -2.8958NM_001166537 // Hmga1 // high mobility group AT-hook 1 // 17 A3.3|17 14.5 cM // 15361 / Hmga1 8.29E-05 -2.90804ENSMUST00000168579 // Slc16a3 // solute carrier family 16 (monocarboxylic acid transpor Slc16a3 8.58E-07 -2.91824NM_021430 // Rilpl1 // Rab interacting lysosomal protein-like 1 // 5|5 F // 75695 /// X Rilpl1 6.44E-07 -2.91906NM_019580 // Gde1 // glycerophosphodiester phosphodiesterase 1 // 7|7 F3 // 56209 /// E Gde1 2.42E-06 -2.9229NM_198861 // Lrrc75a // leucine rich repeat containing 75A // 11 B2|11 // 192976 /// XM Lrrc75a 7.66E-07 -2.92437NM_172728 // Creb5 // cAMP responsive element binding protein 5 // 6 B3|6 25.9 cM // 23 Creb5 1.35E-05 -2.92737NM_001287738 // Cebpb // CCAAT/enhancer binding protein (C/EBP), beta // 2 H3|2 87.58 c Cebpb 7.62E-06 -2.93332NM_001271760 // Adra1a // adrenergic receptor, alpha 1a // 14 D1|14 // 11549 /// NM_001 Adra1a 3.06E-06 -2.93516ENSMUST00000157375 // Gm25493 // predicted gene, 25493 // --- // --- Gm25493 0.000933322 -2.94095NM_080555 // Ppap2b // phosphatidic acid phosphatase type 2B // 4 C6|4 49.18 cM // 6791 Ppap2b 4.36E-06 -2.94101NM_001163833 // Msl3l2 // male-specific lethal 3-like 2 (Drosophila) // 10 B3|10 // 733 Msl3l2 0.000138415 -2.94158NM_009878 // Cdkn2d // cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4) // 9 A Cdkn2d 2.10E-05 -2.94579--- 4.35E-06 -2.94856NM_028287 // Zufsp // zinc finger with UFM1-specific peptidase domain // 10 B1|10 // 72 Zufsp 7.86E-07 -2.94927ENSMUST00000122776 // Gm24141 // predicted gene, 24141 // --- // --- Gm24141 0.00327246 -2.95377NM_025541 // Asf1a // anti-silencing function 1A histone chaperone // 10 B3|10 // 66403 Asf1a 4.88E-06 -2.95638NR_015514 // 9330175E14Rik // RIKEN cDNA 9330175E14 gene // 8 C5|8 // 320377 /// ENSMUS 9330175E14Rik 0.00124518 -2.95989NM_197944 // Hsh2d // hematopoietic SH2 domain containing // 8 B3.3|8 // 209488 /// ENS Hsh2d 6.50E-05 -2.97916ENSMUST00000097355 // 4930403O15Rik // RIKEN cDNA 4930403O15 gene // --- // --- /// AK0 4930403O15Rik 0.00234396 -2.9863NM_172839 // Ccnj // cyclin J // 19 C3|19 // 240665 /// ENSMUST00000025983 // Ccnj // c Ccnj 2.74E-05 -2.98786--- 0.00019928 -2.98883NM_172833 // Malt1 // mucosa associated lymphoid tissue lymphoma translocation gene 1 / Malt1 0.00450255 -2.99553NM_031373 // Ogfr // opioid growth factor receptor // 2 H4|2 // 72075 /// ENSMUST000000 Ogfr 3.93E-07 -3.02452NM_153760 // Mill2 // MHC I like leukocyte 2 // 7 A3|7 9.35 cM // 243864 /// NM_153761 Mill2 0.00064121 -3.02524

NM_029508 // Pcgf5 // polycomb group ring finger 5 // 19 C2|19 // 76073 /// XM_00652743 Pcgf5 0.000296584 -3.03928NM_010333 // S1pr2 // sphingosine-1-phosphate receptor 2 // 9 A3|9 7.68 cM // 14739 /// S1pr2 3.12E-07 -3.04962NM_008967 // Ptgir // prostaglandin I receptor (IP) // 7 A2|7 9.15 cM // 19222 /// XM_0 Ptgir 1.48E-05 -3.05037NM_001290413 // Traf2 // TNF receptor-associated factor 2 // 2 A3|2 // 22030 /// NM_009 Traf2 3.33E-06 -3.06503NM_178890 // Abtb2 // ankyrin repeat and BTB (POZ) domain containing 2 // 2 E2|2 // 993 Abtb2 3.18E-06 -3.06555NM_013671 // Sod2 // superoxide dismutase 2, mitochondrial // 17 A1|17 8.75 cM // 20656 Sod2 0.00107675 -3.07239AK089726 // Trim30a // tripartite motif-containing 30A // 7 E3|7 55.69 cM // 20128 Trim30a 0.00200827 -3.07333ENSMUST00000168990 // Gm17034 // predicted gene 17034 // --- // --- Gm17034 0.00490031 -3.08109NM_011333 // Ccl2 // chemokine (C-C motif) ligand 2 // 11 C-E1|11 49.82 cM // 20296 /// Ccl2 0.00229801 -3.08236NM_145458 // Pxk // PX domain containing serine/threonine kinase // 14 A1|14 4.7 cM // Pxk 1.55E-08 -3.08854NM_016972 // Slc7a8 // solute carrier family 7 (cationic amino acid transporter, y+ sys Slc7a8 2.71E-08 -3.09091XR_375897 // Gm12474 // predicted gene 12474 // 3 F2.2|3 // 545557 /// XR_375898 // Gm1 Gm12474 1.66E-05 -3.09646--- 0.000285409 -3.09826--- 0.00301504 -3.09923--- 0.000233126 -3.10483NM_010156 // Samd9l // sterile alpha motif domain containing 9-like // 6 A1-A2|6 1.76 c Samd9l 3.60E-06 -3.10642NM_145523 // Gca // grancalcin // 2 C1.3|2 // 227960 /// ENSMUST00000028257 // Gca // g Gca 0.0008629 -3.11007NM_001033245 // Hk3 // hexokinase 3 // 13 B1|13 // 212032 /// NM_001206390 // Hk3 // he Hk3 3.04E-08 -3.11156NM_026960 // Gsdmd // gasdermin D // 15|15 D3-E1 // 69146 /// XM_006521343 // Gsdmd // Gsdmd 1.76E-06 -3.12406NM_033541 // Oas1c // 2-5 oligoadenylate synthetase 1C // 5 F|5 60.64 cM // 114643 /// Oas1c 2.62E-06 -3.12673NM_172293 // Pced1b // PC-esterase domain containing 1B // 15 F1|15 // 239647 /// XM_00 Pced1b 0.000809355 -3.12891NM_001040026 // Sco1 // SCO cytochrome oxidase deficient homolog 1 (yeast) // 11 B3|11 Sco1 1.09E-05 -3.13897NM_001033308 // Themis2 // thymocyte selection associated family member 2 // 4 D2.3|4 / Themis2 8.69E-08 -3.14662XR_374962 // Gm14010 // predicted gene 14010 // 2 F1|2 // 100043729 /// ENSMUST00000131 Gm14010 0.00364976 -3.14741NM_145391 // Tapbpl // TAP binding protein-like // 6 F3|6 // 213233 /// XM_006505862 // Tapbpl 0.000276182 -3.14743ENSMUST00000079684 // Gm8394 // predicted gene 8394 // --- // --- Gm8394 1.00E-07 -3.1508NM_010442 // Hmox1 // heme oxygenase (decycling) 1 // 8 C1|8 35.59 cM // 15368 /// ENSM Hmox1 3.28E-07 -3.15669NM_001033450 // Mnda // myeloid cell nuclear differentiation antigen // 1 H3|1 // 38130 Mnda 0.00165775 -3.15731NM_001145979 // Gtpbp2 // GTP binding protein 2 // 17|17 C-D // 56055 /// NM_019581 // Gtpbp2 4.93E-07 -3.16118ENSMUST00000129913 // Igf2bp2 // insulin-like growth factor 2 mRNA binding protein 2 // Igf2bp2 3.75E-06 -3.16564NM_133955 // Rhou // ras homolog gene family, member U // 8 E2|8 // 69581 /// ENSMUST00 Rhou 0.000897679 -3.17878XM_006533108 // Rhbdf2 // rhomboid 5 homolog 2 (Drosophila) // 11 E2|11 // 217344 /// E Rhbdf2 3.12E-06 -3.18049NM_001169131 // Papd7 // PAP associated domain containing 7 // 13 C1|13 35.55 cM // 210 Papd7 2.38E-05 -3.18327NM_011414 // Slpi // secretory leukocyte peptidase inhibitor // 2 H|2 // 20568 /// ENSM Slpi 0.000827033 -3.18369ENSMUST00000139725 // Mitd1 // MIT, microtubule interacting and transport, domain conta Mitd1 1.18E-05 -3.1859NM_001172117 // Hck // hemopoietic cell kinase // 2 H1|2 75.41 cM // 15162 /// NM_01040 Hck 0.000102354 -3.18938NM_010276 // Gem // GTP binding protein (gene overexpressed in skeletal muscle) // 4 A1 Gem 0.00212387 -3.19089NM_183180 // Tspan18 // tetraspanin 18 // 2 E1|2 // 241556 /// XM_006499474 // Tspan18 Tspan18 0.002735 -3.19127NM_001122675 // Zcchc2 // zinc finger, CCHC domain containing 2 // 1 E2.1|1 // 227449 / Zcchc2 3.05E-05 -3.19161NM_010049 // Dhfr // dihydrofolate reductase // 13 C3|13 47.64 cM // 13361 /// ENSMUST0 Dhfr 4.39E-05 -3.19688NM_027411 // Spdl1 // spindle apparatus coiled-coil protein 1 // 11|11 A5 // 70385 /// Spdl1 7.98E-06 -3.20789NM_001081005 // 1500012F01Rik // RIKEN cDNA 1500012F01 gene // 2 H3|2 // 68949 /// ENSM 1500012F01Rik 1.80E-05 -3.21437NM_008842 // Pim1 // proviral integration site 1 // 17 A3.3|17 15.38 cM // 18712 /// EN Pim1 7.02E-05 -3.21791NM_001008497 // P2ry14 // purinergic receptor P2Y, G-protein coupled, 14 // 3 D|3 28.96 P2ry14 1.70E-06 -3.22143NM_134102 // Pla1a // phospholipase A1 member A // 16 B4|16 26.83 cM // 85031 /// XM_00 Pla1a 0.000877393 -3.22149NM_010829 // Msh3 // mutS homolog 3 (E. coli) // 13 C3|13 47.63 cM // 17686 /// XM_0065 Msh3 3.22E-05 -3.2232NM_001145827 // Stk40 // serine/threonine kinase 40 // 4 D2.2|4 // 74178 /// NM_028800 Stk40 3.50E-05 -3.22702NM_001004185 // Whamm // WAS protein homolog associated with actin, golgi membranes and Whamm 8.23E-07 -3.23432NM_009763 // Bst1 // bone marrow stromal cell antigen 1 // 5 B3|5 23.84 cM // 12182 /// Bst1 3.11E-07 -3.23445NR_033498 // AI504432 // expressed sequence AI504432 // 3 F2.3|3 // 229694 /// ENSMUST0 AI504432 0.00317637 -3.23711NM_009807 // Casp1 // caspase 1 // 9 A1|9 2.46 cM // 12362 /// ENSMUST00000027015 // Ca Casp1 2.41E-05 -3.24466NM_029809 // 2310014L17Rik // RIKEN cDNA 2310014L17 gene // 7 A1|7 // 381845 /// ENSMUS 2310014L17Rik 0.00314391 -3.24548NM_001013371 // Dtx3l // deltex 3-like (Drosophila) // 16 B3|16 // 209200 /// ENSMUST00 Dtx3l 1.78E-06 -3.24748NM_001083616 // Cacna1d // calcium channel, voltage-dependent, L type, alpha 1D subunit Cacna1d 1.89E-05 -3.25373NM_023386 // Rtp4 // receptor transporter protein 4 // 16 B1|16 // 67775 /// XM_0065224 Rtp4 9.94E-07 -3.25465NM_008884 // Pml // promyelocytic leukemia // 9 B|9 31.63 cM // 18854 /// NM_178087 // Pml 4.17E-06 -3.26757NM_001038587 // Adar // adenosine deaminase, RNA-specific // 3|3 F2 // 56417 /// NM_001 Adar 5.77E-07 -3.26936NM_001005423 // Mreg // melanoregulin // 1 C3|1 // 381269 /// XM_006496111 // Mreg // m Mreg 0.000302846 -3.27663--- 0.00179902 -3.28184--- 0.00199535 -3.28477NM_013673 // Sp100 // nuclear antigen Sp100 // 1 C5|1 43.6 cM // 20684 /// XM_006529287 Sp100 6.44E-06 -3.28498NM_175648 // Trim30b // tripartite motif-containing 30B // 7 E3|7 // 244183 /// ENSMUST Trim30b 0.000568544 -3.29327--- 0.00327647 -3.29799--- 0.00350455 -3.30007NM_008360 // Il18 // interleukin 18 // 9 A5.3|9 27.75 cM // 16173 /// XM_006510023 // I Il18 0.00016425 -3.30081ENSMUST00000106283 // Rims3 // regulating synaptic membrane exocytosis 3 // 4 D2.2|4 // Rims3 0.000342044 -3.30589NM_007536 // Bcl2a1d // B cell leukemia/lymphoma 2 related protein A1d // 9 E3.1|9 // 1 Bcl2a1d 0.000370551 -3.30744XM_006502252 // Rapgef2 // Rap guanine nucleotide exchange factor (GEF) 2 // 3 E3|3 // Rapgef2 0.000747305 -3.32171NR_045458 // 4933433H22Rik // RIKEN cDNA 4933433H22 gene // 17|17 // 74473 4933433H22Rik 0.000209913 -3.32766NM_010496 // Id2 // inhibitor of DNA binding 2 // 12 B|12 8.57 cM // 15902 /// ENSMUST0 Id2 8.62E-09 -3.3295ENSMUST00000111276 // Slamf7 // SLAM family member 7 // 1|1 H2 // 75345 /// AB196816 // Slamf7 3.16E-05 -3.33385NM_001045481 // Ifi203 // interferon activated gene 203 // 1 H3|1 80.76 cM // 15950 /// Ifi203 2.01E-05 -3.33458NM_017466 // Ccrl2 // chemokine (C-C motif) receptor-like 2 // 9 F|9 60.92 cM // 54199 Ccrl2 0.000580599 -3.34799NM_008328 // Ifi203 // interferon activated gene 203 // 1 H3|1 80.76 cM // 15950 /// EN Ifi203 8.12E-05 -3.35449NM_175401 // Fbxw17 // F-box and WD-40 domain protein 17 // 13 A5|13 // 109082 /// XM_0 Fbxw17 1.31E-08 -3.35926--- 1.71E-05 -3.36288ENSMUST00000102409 // Gm24049 // predicted gene, 24049 // --- // --- Gm24049 0.00205167 -3.3647NM_133217 // Bco2 // beta-carotene oxygenase 2 // 9|9 B // 170752 /// XM_006510045 // B Bco2 0.0013708 -3.36828NM_019915 // Art2b // ADP-ribosyltransferase 2b // 7 E3|7 54.61 cM // 11872 /// XM_0065 Art2b 0.00513279 -3.36856NM_001081005 // 1500012F01Rik // RIKEN cDNA 1500012F01 gene // 2 H3|2 // 68949 /// ENSM 1500012F01Rik 1.35E-06 -3.40877NM_008367 // Il2ra // interleukin 2 receptor, alpha chain // 2 A2-A3|2 8.91 cM // 16184 Il2ra 0.0010101 -3.42186NM_175382 // Fam72a // family with sequence similarity 72, member A // 1 E4|1 // 108900 Fam72a 1.69E-05 -3.42598NM_013673 // Sp100 // nuclear antigen Sp100 // 1 C5|1 43.6 cM // 20684 /// XM_006529287 Sp100 2.57E-05 -3.42811NM_001252568 // Phyhd1 // phytanoyl-CoA dioxygenase domain containing 1 // 2 B|2 // 227 Phyhd1 7.25E-05 -3.4436NM_001163489 // Sema4a // sema domain, immunoglobulin domain (Ig), transmembrane domain Sema4a 3.19E-09 -3.44711NM_001164566 // Spats2l // spermatogenesis associated, serine-rich 2-like // 1|1 C2 // Spats2l 0.00347238 -3.44873NM_001253817 // Tmem184b // transmembrane protein 184b // 15 E1|15 // 223693 /// NM_001 Tmem184b 1.70E-07 -3.45596XM_006517419 // Slc6a19 // solute carrier family 6 (neurotransmitter transporter), memb Slc6a19 0.000357784 -3.46428--- 2.85E-06 -3.46462NM_025446 // Aig1 // androgen-induced 1 // 10 A2|10 // 66253 /// ENSMUST00000019942 // Aig1 7.37E-06 -3.46555NM_001168334 // Gm2799 // predicted gene 2799 // X A3.1|X // 100040482 /// ENSMUST00000 Gm2799 0.000161184 -3.47244--- 0.00245377 -3.47887XM_006497078 // LOC102639543 // pyrin domain-containing protein 3-like // --- // 102639 LOC102639543 0.00173044 -3.48243ENSMUST00000111360 // LOC100041057 // nuclear body protein SP140-like // 1|1 // 1000410 LOC100041057 0.00219959 -3.48316NM_025659 // Abi3 // ABI gene family, member 3 // 11 D|11 // 66610 /// XM_006533953 // Abi3 1.76E-06 -3.49087

NM_001198765 // Postn // periostin, osteoblast specific factor // 3 C|3 // 50706 /// NM Postn 3.03E-05 -3.49613ENSMUST00000029140 // Procr // protein C receptor, endothelial // 2|2 H1-3 // 19124 /// Procr 5.03E-06 -3.50157NM_010186 // Fcgr1 // Fc receptor, IgG, high affinity I // 3 F2.1|3 41.72 cM // 14129 / Fcgr1 6.10E-07 -3.50343NM_001111304 // Tbc1d9 // TBC1 domain family, member 9 // 8|8 C3 // 71310 /// NM_027758 Tbc1d9 8.36E-09 -3.5102NM_023731 // Ccdc86 // coiled-coil domain containing 86 // 19 B|19 7.41 cM // 108673 // Ccdc86 3.25E-05 -3.51466NR_030251 // Mir483 // microRNA 483 // 7|7 // 723874 /// ENSMUST00000093631 // Mir483 / Mir483 0.000803811 -3.52225NR_030251 // Mir483 // microRNA 483 // 7|7 // 723874 /// ENSMUST00000093631 // Mir483 / Mir483 0.000803811 -3.52225XM_006497081 // Gm16340 // predicted gene 16340 // 1|1 80.65 cM // 100504287 /// ENSMUS Gm16340 0.000231527 -3.52596NM_181344 // C1rl // complement component 1, r subcomponent-like // 6 F2|6 // 232371 // C1rl 9.36E-08 -3.52718NM_001290475 // Tdrd7 // tudor domain containing 7 // 4 B1|4 // 100121 /// NM_146142 // Tdrd7 8.69E-07 -3.52765NM_145968 // Tagap // T cell activation Rho GTPase activating protein // 17 A1|17 // 72 Tagap 0.00043789 -3.5501NM_172785 // Zc3h12d // zinc finger CCCH type containing 12D // 10 A1|10 // 237256 /// Zc3h12d 4.11E-05 -3.58021NM_001289568 // Sass6 // spindle assembly 6 homolog (C. elegans) // 3|3 G2 // 72776 /// Sass6 0.000132573 -3.58829NM_133954 // Usb1 // U6 snRNA biogenesis 1 // 8 D1|8 // 101985 /// ENSMUST00000034245 / Usb1 1.59E-06 -3.60149NM_133821 // Phlpp1 // PH domain and leucine rich repeat protein phosphatase 1 // 1 E2. Phlpp1 4.81E-06 -3.61318NM_011409 // Slfn3 // schlafen 3 // 11 C|11 // 20557 /// XM_006532656 // Slfn3 // schla Slfn3 4.94E-05 -3.61601--- 0.000754005 -3.63036NM_001004157 // Scarf1 // scavenger receptor class F, member 1 // 11 B5|11 // 380713 // Scarf1 5.85E-05 -3.63821NM_175236 // Adhfe1 // alcohol dehydrogenase, iron containing, 1 // 1 A2|1 // 76187 /// Adhfe1 2.68E-05 -3.64459NM_013875 // Pde7b // phosphodiesterase 7B // 10 A3|10 // 29863 /// XM_006512758 // Pde Pde7b 5.02E-07 -3.69568NM_013632 // Pnp // purine-nucleoside phosphorylase // 14 B-C1|14 26.31 cM // 18950 /// Pnp 2.69E-05 -3.69956NM_030253 // Parp9 // poly (ADP-ribose) polymerase family, member 9 // 16 B3|16 // 8028 Parp9 2.47E-06 -3.70141NM_028019 // Rnf135 // ring finger protein 135 // 11 B5|11 47.59 cM // 71956 /// ENSMUS Rnf135 3.60E-06 -3.70832NM_008607 // Mmp13 // matrix metallopeptidase 13 // 9|9 A1-A2 // 17386 /// ENSMUST00000 Mmp13 0.00455139 -3.71477NR_073523 // Slfn10-ps // schlafen 10, pseudogene // 11 C|11 // 237887 /// NR_073524 // Slfn10-ps 5.51E-05 -3.72815NM_001039562 // Ankrd37 // ankyrin repeat domain 37 // 8 B1.1|8 // 654824 /// ENSMUST00 Ankrd37 8.42E-05 -3.72951XR_376538 // LOC102635290 // uncharacterized LOC102635290 // --- // 102635290 /// XR_37 LOC102635290 1.93E-06 -3.76778NM_001204910 // AI607873 // expressed sequence AI607873 // 1 H3|1 // 226691 /// ENSMUST AI607873 0.000280158 -3.78015NM_001033632 // Ifitm6 // interferon induced transmembrane protein 6 // 7 F5|7 // 21300 Ifitm6 2.71E-05 -3.78413NR_038025 // 4933412E12Rik // RIKEN cDNA 4933412E12 gene // 10|10 // 71086 /// NR_03802 4933412E12Rik 0.000588597 -3.79181ENSMUST00000120177 // Gstt1 // glutathione S-transferase, theta 1 // 10 B5-C1|10 38.58 Gstt1 7.74E-06 -3.82939--- 9.35E-06 -3.8294NM_177861 // Tmem67 // transmembrane protein 67 // 4 A1|4 // 329795 /// NR_110955 // Tm Tmem67 1.00E-05 -3.83143NM_026985 // Mcemp1 // mast cell expressed membrane protein 1 // 8 A1|8 1.92 cM // 6918 Mcemp1 0.000205747 -3.83643NM_194346 // Rnf31 // ring finger protein 31 // 14 C3|14 // 268749 /// ENSMUST000000194 Rnf31 1.23E-06 -3.85626NM_145373 // Sectm1a // secreted and transmembrane 1A // 11 E2|11 // 209588 /// XM_0065 Sectm1a 6.35E-06 -3.86014NM_126166 // Tlr3 // toll-like receptor 3 // 8|8 B2 // 142980 /// XM_006509278 // Tlr3 Tlr3 3.45E-05 -3.86121NM_009930 // Col3a1 // collagen, type III, alpha 1 // 1 C1.1|1 23.67 cM // 12825 /// EN Col3a1 6.87E-05 -3.87022NM_001161770 // Lmo4 // LIM domain only 4 // 3 H2|3 68.61 cM // 16911 /// ENSMUST000001 Lmo4 1.40E-06 -3.87171NR_045146 // BC051226 // cDNA sequence BC051226 // 17 B1|17 // 407803 /// ENSMUST000001 BC051226 4.90E-06 -3.87747ENSMUST00000160674 // Csprs // component of Sp100-rs // 8 B1.3|1 // 114564 /// ENSMUST0 Csprs 3.68E-05 -3.88243NM_146064 // Soat2 // sterol O-acyltransferase 2 // 15 F3|15 57.33 cM // 223920 /// XM_ Soat2 0.000273837 -3.89195NM_010724 // Psmb8 // proteasome (prosome, macropain) subunit, beta type 8 (large multi Psmb8 3.26E-08 -3.89385NM_001013616 // Trim6 // tripartite motif-containing 6 // 7 F1|7 55.55 cM // 94088 /// Trim6 0.000118752 -3.91431XR_390079 // LOC102634822 // uncharacterized LOC102634822 // --- // 102634822 /// XR_40 LOC102634822 0.000195999 -3.92183NM_013558 // Hspa1l // heat shock protein 1-like // 17 B1|17 18.51 cM // 15482 /// ENSM Hspa1l 0.00301875 -3.93412NM_001002898 // Sirpb1a // signal-regulatory protein beta 1A // 3 A1|3 // 320832 /// EN Sirpb1a 0.000197586 -3.93885NM_001025246 // Trp53i11 // transformation related protein 53 inducible protein 11 // 2 Trp53i11 0.000334662 -3.95662NM_007742 // Col1a1 // collagen, type I, alpha 1 // 11 D|11 59.01 cM // 12842 /// ENSMU Col1a1 2.99E-06 -3.96343ENSMUST00000103475 // Ighv14-4 // immunoglobulin heavy variable 14-4 // --- // --- /// Ighv14-4 0.0021995 -3.97979NM_139269 // Pla2g16 // phospholipase A2, group XVI // 19 A|19 // 225845 /// XM_0065269 Pla2g16 0.000290173 -3.98505ENSMUST00000093902 // Rnf213 // ring finger protein 213 // 11 E2|11 83.48 cM // 672511 Rnf213 0.000260859 -4.01613XM_006496589 // LOC101056250 // sp110 nuclear body protein-like // --- // 101056250 /// LOC101056250 3.29E-05 -4.02587NM_008206 // H2-Oa // histocompatibility 2, O region alpha locus // 17 B1|17 17.98 cM / H2-Oa 0.00083914 -4.05266NM_013825 // Ly75 // lymphocyte antigen 75 // 2 C1.1|2 // 17076 /// ENSMUST00000028362 Ly75 5.07E-06 -4.05775NM_011530 // Tap2 // transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) // 17 Tap2 3.38E-08 -4.05894NM_029472 // Gstt4 // glutathione S-transferase, theta 4 // 10 C1|10 // 75886 /// ENSMU Gstt4 0.000234143 -4.06154NM_010959 // Oit3 // oncoprotein induced transcript 3 // 10|10 B3 // 18302 /// ENSMUST0 Oit3 1.14E-07 -4.06408NM_001012236 // Trex1 // three prime repair exonuclease 1 // 9 F2|9 // 22040 /// NM_011 Trex1 1.39E-05 -4.06789NM_001035228 // St3gal5 // ST3 beta-galactoside alpha-2,3-sialyltransferase 5 // 6|6 C3 St3gal5 2.47E-07 -4.07571NM_013822 // Jag1 // jagged 1 // 2 F3|2 67.73 cM // 16449 /// ENSMUST00000028735 // Jag Jag1 6.02E-07 -4.082NM_013754 // Insl6 // insulin-like 6 // 19|19 C3 // 27356 /// ENSMUST00000052380 // Ins Insl6 5.98E-06 -4.08907NM_145227 // Oas2 // 2-5 oligoadenylate synthetase 2 // 5 F|5 60.64 cM // 246728 /// XM Oas2 5.00E-06 -4.09634NM_011854 // Oasl2 // 2-5 oligoadenylate synthetase-like 2 // 5 F|5 // 23962 /// ENSMUS Oasl2 1.19E-05 -4.10281XM_006496589 // LOC101056250 // sp110 nuclear body protein-like // --- // 101056250 /// LOC101056250 8.62E-05 -4.1096--- 0.00149029 -4.11467NM_010484 // Slc6a4 // solute carrier family 6 (neurotransmitter transporter, serotonin Slc6a4 2.66E-06 -4.12045NM_021398 // Slc43a3 // solute carrier family 43, member 3 // 2 E1|2 // 58207 /// XM_00 Slc43a3 1.07E-06 -4.12147NR_004446 // H2-K2 // histocompatibility 2, K region locus 2 // 17 B1|17 17.98 cM // 63 H2-K2 0.000328045 -4.12775NM_008207 // H2-T24 // histocompatibility 2, T region locus 24 // 17 B1|17 18.84 cM // H2-T24 7.86E-05 -4.12843NM_022982 // Rtn4r // reticulon 4 receptor // 16 B1|16 // 65079 /// ENSMUST00000059589 Rtn4r 3.06E-06 -4.13618NM_008608 // Mmp14 // matrix metallopeptidase 14 (membrane-inserted) // 14 C2|14 27.79 Mmp14 0.000434539 -4.15948--- 1.71E-05 -4.16551XM_006544847 // LOC102642448 // schlafen family member 13-like // --- // 102642448 /// LOC102642448 6.27E-06 -4.16646NM_008216 // Has2 // hyaluronan synthase 2 // 15 D1|15 23.31 cM // 15117 /// ENSMUST000 Has2 2.16E-07 -4.17085NR_033804 // Art2a-ps // ADP-ribosyltransferase 2a, pseudogene // 7 E3|7 54.6 cM // 118 Art2a-ps 0.000107028 -4.18045NM_001163645 // Osbpl3 // oxysterol binding protein-like 3 // 6|6 B3 // 71720 /// NM_02 Osbpl3 1.62E-06 -4.18628NM_001205053 // Jdp2 // Jun dimerization protein 2 // 12|12 D3 // 81703 /// NM_030887 / Jdp2 0.000294276 -4.18732--- 0.00170086 -4.19432NM_029803 // Ifi27l2a // interferon, alpha-inducible protein 27 like 2A // 12 E|12 // 7 Ifi27l2a 2.47E-05 -4.20999ENSMUST00000046739 // Ifi44l // interferon-induced protein 44 like // 3 H3|3 76.94 cM / Ifi44l 0.000295429 -4.21019NM_181402 // Parp11 // poly (ADP-ribose) polymerase family, member 11 // 6 F3|6 // 1011 Parp11 5.67E-06 -4.23537NM_009256 // Serpinb9 // serine (or cysteine) peptidase inhibitor, clade B, member 9 // Serpinb9 2.74E-07 -4.24001--- 1.30E-05 -4.24123NM_001113379 // Lrrc32 // leucine rich repeat containing 32 // 7 E2|7 53.86 cM // 43421 Lrrc32 1.11E-05 -4.24304NM_001173460 // Sirpb1b // signal-regulatory protein beta 1B // 3 A1|3 // 668101 /// XM Sirpb1b 3.01E-06 -4.24787ENSMUST00000181444 // Gm26589 // predicted gene, 26589 // --- // --- /// XR_379475 // L Gm26589 6.62E-06 -4.25334NM_027482 // 5730508B09Rik // RIKEN cDNA 5730508B09 gene // 3|3 H1 // 70617 /// ENSMUST 5730508B09Rik 0.000455534 -4.26705NM_172689 // Ddx58 // DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 // 4 A5|4 // 230073 /// Ddx58 2.81E-05 -4.26729ENSMUST00000116345 // Gm17193 // predicted gene 17193 // --- // --- Gm17193 1.12E-05 -4.2831XM_006535876 // LOC677525 // sp110 nuclear body protein-like // 1|1 // 677525 /// NM_03 LOC677525 6.17E-05 -4.32505ENSMUST00000032961 // Nupr1 // nuclear protein transcription regulator 1 // 7 F4|7 // 5 Nupr1 1.24E-06 -4.35263NM_024495 // Car13 // carbonic anhydrase 13 // 3|3 A2 // 71934 /// ENSMUST00000029071 / Car13 2.69E-05 -4.36196NM_023141 // Tor3a // torsin family 3, member A // 1 H1|1 // 30935 /// ENSMUST000000796 Tor3a 5.03E-06 -4.38955NM_001110320 // Cd72 // CD72 antigen // 4 B1|4 23.04 cM // 12517 /// NM_007654 // Cd72 Cd72 1.98E-07 -4.42011

NM_001141948 // Nmi // N-myc (and STAT) interactor // 2|2 C1 // 64685 /// NM_001141949 Nmi 7.63E-06 -4.43269NM_053108 // Glrx // glutaredoxin // 13 C1|13 40.95 cM // 93692 /// ENSMUST00000022082 Glrx 2.04E-05 -4.43541NM_001025395 // Src // Rous sarcoma oncogene // 2 H1|2 78.35 cM // 20779 /// NM_009271 Src 3.29E-05 -4.50004NM_001013817 // Sp140 // Sp140 nuclear body protein // 1 C5|1 // 434484 /// NM_00103790 Sp140 8.98E-06 -4.5092NM_011930 // Clcn7 // chloride channel 7 // 17 A3.3|17 12.53 cM // 26373 /// ENSMUST000 Clcn7 6.21E-07 -4.52478--- 2.12E-05 -4.52915NM_213615 // A530032D15Rik // RIKEN cDNA A530032D15Rik gene // 1 C5|1 // 381287 /// ENS A530032D15Rik 4.54E-06 -4.54266NM_009767 // Chic1 // cysteine-rich hydrophobic domain 1 // X D|X 42.3 cM // 12212 /// Chic1 3.51E-06 -4.54985ENSMUST00000023341 // Cd200 // CD200 antigen // 16 A1|16 29.53 cM // 17470 /// ENSMUST0 Cd200 5.83E-05 -4.55198NM_145211 // Oas1a // 2-5 oligoadenylate synthetase 1A // 5 F|5 60.65 cM // 246730 /// Oas1a 3.40E-05 -4.57929NR_045750 // Gm16675 // predicted gene, 16675 // 8|8 26.42 cM // 100503498 /// ENSMUST0 Gm16675 2.56E-06 -4.64852NM_008327 // Ifi202b // interferon activated gene 202B // 1 H3|1 // 26388 /// NM_011940 Ifi202b 1.14E-05 -4.66947NM_001254747 // Il15 // interleukin 15 // 8 C2|8 39.33 cM // 16168 /// NM_008357 // Il1 Il15 0.0001345 -4.68276NM_001170851 // Klra2 // killer cell lectin-like receptor, subfamily A, member 2 // 6 F Klra2 7.03E-05 -4.70233NM_175093 // Trib3 // tribbles homolog 3 (Drosophila) // 2 G3|2 74.83 cM // 228775 /// Trib3 3.93E-06 -4.70671NM_001290183 // Ddit3 // DNA-damage inducible transcript 3 // 10 D3|10 // 13198 /// NM_ Ddit3 3.83E-06 -4.71294ENSMUST00000121995 // Gm15821 // predicted gene 15821 // 17|17 17.98 cM // 100502931 // Gm15821 3.78E-05 -4.72922NM_001013817 // Sp140 // Sp140 nuclear body protein // 1 C5|1 // 434484 /// ENSMUST0000 Sp140 0.000788487 -4.74543NM_001085385 // 1600014C10Rik // RIKEN cDNA 1600014C10 gene // 7|7 B1 // 72244 /// ENSM 1600014C10Rik 4.32E-09 -4.75169NM_133888 // Smpdl3b // sphingomyelin phosphodiesterase, acid-like 3B // 4 D2.3|4 // 10 Smpdl3b 1.53E-05 -4.76839ENSMUST00000180685 // Gm26797 // predicted gene, 26797 // --- // --- Gm26797 0.000154965 -4.78391--- 0.000132551 -4.7846--- 0.000132551 -4.7846NM_001033207 // Nlrc5 // NLR family, CARD domain containing 5 // 8 C5|8 // 434341 /// X Nlrc5 0.000329578 -4.78862NM_001082552 // Trim21 // tripartite motif-containing 21 // 7 F1|7 // 20821 /// NM_0092 Trim21 5.82E-05 -4.80012ENSMUST00000136366 // Ms4a4b // membrane-spanning 4-domains, subfamily A, member 4B // Ms4a4b 0.00220551 -4.82228NM_008479 // Lag3 // lymphocyte-activation gene 3 // 6 F2|6 // 16768 /// ENSMUST0000003 Lag3 2.14E-05 -4.83833NM_001172205 // Arid5a // AT rich interactive domain 5A (MRF1-like) // 1 B|1 // 214855 Arid5a 2.63E-06 -4.84493--- 1.62E-05 -4.86639--- 1.62E-05 -4.86639NM_172893 // Parp12 // poly (ADP-ribose) polymerase family, member 12 // 6 B1|6 // 2437 Parp12 1.60E-05 -4.87645NM_008102 // Gch1 // GTP cyclohydrolase 1 // 14 C2-3|14 24.6 cM // 14528 /// ENSMUST000 Gch1 1.28E-06 -4.89172NR_045367 // A630012P03Rik // RIKEN cDNA A630012P03 gene // X A5|X // 100504594 /// ENS A630012P03Rik 6.77E-06 -4.89861NM_172883 // Mfsd7a // major facilitator superfamily domain containing 7A // 5 F|5 // 2 Mfsd7a 3.02E-06 -4.95515NM_153511 // Il1f9 // interleukin 1 family, member 9 // 2 A3|2 16.24 cM // 215257 /// E Il1f9 0.000114605 -4.97272NM_008655 // Gadd45b // growth arrest and DNA-damage-inducible 45 beta // 10 C1|10 39.7 Gadd45b 1.68E-06 -4.97651ENSMUST00000173680 // Gm20481 // predicted gene 20481 // --- // --- /// BC054065 // Hsp Gm20481 1.09E-05 -4.99032NM_001177752 // Pfkfb3 // 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 // 2 A1 Pfkfb3 7.98E-06 -4.99741NM_007609 // Casp4 // caspase 4, apoptosis-related cysteine peptidase // 9 A1|9 2.46 cM Casp4 4.78E-05 -5.02559NM_019949 // Ube2l6 // ubiquitin-conjugating enzyme E2L 6 // 2|2 E1 // 56791 /// ENSMUS Ube2l6 2.87E-06 -5.03852NM_023738 // Uba7 // ubiquitin-like modifier activating enzyme 7 // 9 F2|9 59.07 cM // Uba7 5.50E-07 -5.05669XM_006537281 // Psmb9 // proteasome (prosome, macropain) subunit, beta type 9 (large mu Psmb9 7.32E-07 -5.06058ENSMUST00000142107 // Gm11626 // predicted gene 11626 // --- // --- Gm11626 0.000302063 -5.06895NM_029522 // Gpsm2 // G-protein signalling modulator 2 (AGS3-like, C. elegans) // 3 F3| Gpsm2 6.59E-07 -5.07121NM_138953 // Ell2 // elongation factor RNA polymerase II 2 // 13 C1|13 // 192657 /// EN Ell2 1.58E-06 -5.07632NM_008311 // Htr2b // 5-hydroxytryptamine (serotonin) receptor 2B // 1 C5|1 // 15559 // Htr2b 2.26E-06 -5.09236NM_023456 // Npy // neuropeptide Y // 6 B3|6 24.04 cM // 109648 /// ENSMUST00000031843 Npy 4.11E-05 -5.11978NR_102296 // C430002N11Rik // RIKEN cDNA C430002N11 gene // 9|9 // 319707 /// NR_102293 C430002N11Rik 0.000451615 -5.1209ENSMUST00000108349 // LOC100038947 // signal-regulatory protein beta 1-like // 3 A1|3 / LOC100038947 0.00142378 -5.1267NM_010531 // Il18bp // interleukin 18 binding protein // 7|7 F1 // 16068 /// ENSMUST000 Il18bp 6.99E-07 -5.12874NM_007832 // Dck // deoxycytidine kinase // 5 E2|5 // 13178 /// ENSMUST00000031311 // D Dck 1.08E-06 -5.15303BC128471 // Unc93a // unc-93 homolog A (C. elegans) // 17 A1|17 8.78 cM // 381058 /// N Unc93a 0.000402219 -5.15966NM_008329 // Ifi204 // interferon activated gene 204 // 1 H3|1 80.63 cM // 15951 /// XM Ifi204 0.000420141 -5.16491NM_021887 // Il21r // interleukin 21 receptor // 7|7 F4 // 60504 /// XM_006508097 // Il Il21r 4.38E-08 -5.16695NM_001004762 // Pla2g4c // phospholipase A2, group IVC (cytosolic, calcium-independent) Pla2g4c 0.000203398 -5.18152NM_010398 // H2-T23 // histocompatibility 2, T region locus 23 // 17 B1|17 18.86 cM // H2-T23 8.46E-07 -5.20484--- 0.00142095 -5.20652NM_001205313 // Stat1 // signal transducer and activator of transcription 1 // 1 C1.1|1 Stat1 1.04E-05 -5.20773NM_011817 // Gadd45g // growth arrest and DNA-damage-inducible 45 gamma // 13|13 A5-B / Gadd45g 2.94E-08 -5.27326--- 0.00020246 -5.2747XR_378400 // Gm8995 // predicted gene 8995 // 7 E3|7 // 668139 /// ENSMUST00000184842 / Gm8995 9.65E-06 -5.3384NR_030719 // Gm8979 // very large inducible GTPase 1 pseudogene // 7 E3|7 // 668108 /// Gm8979 2.16E-05 -5.35696NM_001008233 // Plekhn1 // pleckstrin homology domain containing, family N member 1 // Plekhn1 6.82E-07 -5.38336XM_006535862 // LOC100041708 // nuclear body protein SP140-like // 1|1 // 100041708 LOC100041708 0.000450999 -5.38792--- 0.000331031 -5.40782NM_153287 // Csrnp1 // cysteine-serine-rich nuclear protein 1 // 9 F4|9 // 215418 /// X Csrnp1 5.31E-08 -5.45173NM_001164477 // Ifih1 // interferon induced with helicase C domain 1 // 2|2 C3 // 71586 Ifih1 0.000399031 -5.45699NM_001177576 // Slc25a22 // solute carrier family 25 (mitochondrial carrier, glutamate) Slc25a22 1.16E-07 -5.46451ENSMUST00000162784 // Gm16094 // predicted gene 16094 // --- // --- Gm16094 0.000132341 -5.49349NM_013484 // C2 // complement component 2 (within H-2S) // 17 B1|17 18.41 cM // 12263 / C2 0.000287264 -5.54593NR_030719 // Gm8979 // very large inducible GTPase 1 pseudogene // 7 E3|7 // 668108 /// Gm8979 1.31E-05 -5.56077NM_008326 // Irgm1 // immunity-related GTPase family M member 1 // 11 B1.2|11 // 15944 Irgm1 2.72E-06 -5.57144NM_145530 // Rhov // ras homolog gene family, member V // 2 E5|2 // 228543 /// ENSMUST0 Rhov 8.47E-09 -5.57695NM_001161798 // Mthfr // 5,10-methylenetetrahydrofolate reductase // 4 E2|4 78.67 cM // Mthfr 2.60E-07 -5.57742NM_009775 // Tspo // translocator protein // 15 E1|15 39.4 cM // 12257 /// ENSMUST00000 Tspo 6.73E-07 -5.61282ENSMUST00000103468 // Igh-V11 // immunoglobulin heavy chain (V11 family) // 12 F1|12 // Igh-V11 0.000175222 -5.61559--- 0.00552939 -5.64947NM_138682 // Lrrc4 // leucine rich repeat containing 4 // 6 A3.3|6 // 192198 /// ENSMUS Lrrc4 1.44E-05 -5.65896AK035387 // Gm20559 // predicted gene, 20559 // 6 A1|6 // 330256 Gm20559 5.36E-07 -5.68786NM_008380 // Inhba // inhibin beta-A // 13 A1|13 5.85 cM // 16323 /// ENSMUST0000004260 Inhba 6.27E-06 -5.69569NM_009801 // Car2 // carbonic anhydrase 2 // 3 A1|3 3.23 cM // 12349 /// XM_006530050 / Car2 0.000945506 -5.765NM_001033196 // Znfx1 // zinc finger, NFX1-type containing 1 // 2 H3|2 // 98999 /// ENS Znfx1 1.96E-07 -5.76508NM_010577 // Itga5 // integrin alpha 5 (fibronectin receptor alpha) // 15 F3|15 58.9 cM Itga5 2.30E-06 -5.76673ENSMUST00000172979 // H2-Q5 // histocompatibility 2, Q region locus 5 // 17 B1|17 19.17 H2-Q5 4.88E-05 -5.77922NM_009742 // Bcl2a1a // B cell leukemia/lymphoma 2 related protein A1a // 9 E3.1|9 47.2 Bcl2a1a 0.000692464 -5.8292NM_010597 // Kcnab1 // potassium voltage-gated channel, shaker-related subfamily, beta Kcnab1 2.61E-08 -5.83047NM_028788 // 1300002K09Rik // RIKEN cDNA 1300002K09 gene // 4 B1|4 // 74152 /// XM_0065 1300002K09Rik 9.55E-08 -5.9135NM_009630 // Adora2a // adenosine A2a receptor // 10 B5.3|10 // 11540 /// XM_006513094 Adora2a 0.00448167 -5.92243NM_001033780 // I830077J02Rik // RIKEN cDNA I830077J02 gene // 3 F2.2|3 // 433638 /// X I830077J02Rik 1.02E-08 -5.93977NM_010231 // Fmo1 // flavin containing monooxygenase 1 // 1 H1|1 70.34 cM // 14261 /// Fmo1 3.19E-06 -6.00666NM_001038643 // Slco3a1 // solute carrier organic anion transporter family, member 3a1 Slco3a1 0.00019235 -6.0429NM_001161790 // Mefv // Mediterranean fever // 16 A1|16 2.18 cM // 54483 /// NM_0011617 Mefv 0.00126195 -6.04635NM_007707 // Socs3 // suppressor of cytokine signaling 3 // 11 E2|11 // 12702 /// ENSMU Socs3 0.00152061 -6.06688NM_001171007 // Nod1 // nucleotide-binding oligomerization domain containing 1 // 6 B3| Nod1 7.04E-06 -6.08349NM_176922 // Itga11 // integrin alpha 11 // 9 B|9 // 319480 /// ENSMUST00000034774 // I Itga11 1.52E-06 -6.11941

NM_025658 // Ms4a4d // membrane-spanning 4-domains, subfamily A, member 4D // 19 A|19 / Ms4a4d 6.55E-05 -6.2106NM_001199733 // Daxx // Fas death domain-associated protein // 17 B1|17 17.98 cM // 131 Daxx 2.70E-05 -6.21615NM_001198835 // Coch // coagulation factor C homolog (Limulus polyphemus) // 12 C1|12 2 Coch 5.06E-06 -6.2779NM_001102404 // Acp5 // acid phosphatase 5, tartrate resistant // 9 A3|9 8.38 cM // 114 Acp5 9.37E-07 -6.28295NM_011141 // Pou3f1 // POU domain, class 3, transcription factor 1 // 4 D2.2|4 57.86 cM Pou3f1 3.96E-05 -6.36706XM_006514332 // Misp // mitotic spindle positioning // 10 C1|10 // 78906 /// XM_0065143 Misp 8.99E-06 -6.36845ENSMUST00000111253 // Setdb2 // SET domain, bifurcated 2 // 14 C3|14 // 239122 /// AK08 Setdb2 2.01E-06 -6.38708NM_175118 // Dusp28 // dual specificity phosphatase 28 // 1 D|1 // 67446 /// ENSMUST000 Dusp28 6.29E-06 -6.41692NM_001161730 // Tap1 // transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) // Tap1 7.14E-06 -6.41798NM_009776 // Serping1 // serine (or cysteine) peptidase inhibitor, clade G, member 1 // Serping1 8.83E-06 -6.44144NM_030150 // Dhx58 // DEXH (Asp-Glu-X-His) box polypeptide 58 // 11 D|11 63.52 cM // 80 Dhx58 5.12E-07 -6.46261NM_001142952 // Fam46c // family with sequence similarity 46, member C // 3 F2.2|3 // 7 Fam46c 3.72E-07 -6.47253NM_011852 // Oas1g // 2-5 oligoadenylate synthetase 1G // 5 F|5 60.65 cM // 23960 /// E Oas1g 1.80E-05 -6.49644NM_010510 // Ifnb1 // interferon beta 1, fibroblast // 4 C4|4 41.91 cM // 15977 /// ENS Ifnb1 6.25E-08 -6.51255NM_172796 // Slfn9 // schlafen 9 // 11 C|11 // 237886 /// ENSMUST00000038211 // Slfn9 / Slfn9 0.000199195 -6.53247NM_001045540 // Gm12185 // predicted gene 12185 // 11 B1.2|11 // 620913 /// ENSMUST0000 Gm12185 0.000112523 -6.68304NM_009156 // Sepw1 // selenoprotein W, muscle 1 // 7|7 A2 // 20364 /// ENSMUST000000443 Sepw1 1.89E-07 -6.80992NM_008638 // Mthfd2 // methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methen Mthfd2 2.43E-08 -6.81168NM_001271603 // Socs1 // suppressor of cytokine signaling 1 // 16 A1|16 5.81 cM // 1270 Socs1 0.00035446 -6.88565NM_001136082 // Timeless // timeless circadian clock 1 // 10 D3|10 76.49 cM // 21853 // Timeless 4.68E-07 -6.89628NM_008247 // Ppap2a // phosphatidic acid phosphatase type 2A // 13 D2.2|13 // 19012 /// Ppap2a 1.37E-07 -6.89676ENSMUST00000134150 // Batf2 // basic leucine zipper transcription factor, ATF-like 2 // Batf2 2.26E-05 -6.94138NM_001045526 // Scimp // SLP adaptor and CSK interacting membrane protein // 11 B3|11 / Scimp 5.56E-05 -7.00053NM_009728 // Atp10a // ATPase, class V, type 10A // 7 C|7 // 11982 /// XM_006540582 // Atp10a 0.000179495 -7.0125NM_010397 // H2-T22 // histocompatibility 2, T region locus 22 // 17 B1|17 18.87 cM // H2-T22 1.97E-06 -7.01566NM_008013 // Fgl2 // fibrinogen-like protein 2 // 5 A3|5 9.83 cM // 14190 /// ENSMUST00 Fgl2 9.95E-05 -7.02083NM_001101475 // F830016B08Rik // RIKEN cDNA F830016B08 gene // 18 D3|18 // 240328 /// X F830016B08Rik 0.0017214 -7.03144NM_027320 // Ifi35 // interferon-induced protein 35 // 11 D|11 // 70110 /// ENSMUST0000 Ifi35 2.52E-06 -7.04166NM_011562 // Tdgf1 // teratocarcinoma-derived growth factor 1 // 9 F3|9 60.79 cM // 216 Tdgf1 6.27E-05 -7.07191NR_040453 // Gm17757 // GTPase, very large interferon inducible 1 pseudogene // 7|7 // Gm17757 0.000140179 -7.08871NM_001163440 // Mov10 // Moloney leukemia virus 10 // 3|3 F2 // 17454 /// NM_001163441 Mov10 1.81E-06 -7.11255NM_001271676 // Ifi47 // interferon gamma inducible protein 47 // 11 B1.2|11 // 15953 / Ifi47 0.000153421 -7.12242NM_001163575 // Parp10 // poly (ADP-ribose) polymerase family, member 10 // 15 D3|15 // Parp10 1.94E-07 -7.13469NM_019963 // Stat2 // signal transducer and activator of transcription 2 // 10 D3|10 76 Stat2 9.73E-06 -7.16562NM_029495 // Epsti1 // epithelial stromal interaction 1 (breast) // 14 D3|14 // 108670 Epsti1 7.62E-05 -7.1688NM_175449 // Fam26f // family with sequence similarity 26, member F // 10 B1|10 // 2159 Fam26f 0.00116948 -7.18224NM_001252374 // Nt5c3 // 5-nucleotidase, cytosolic III // 6 B3|6 // 107569 /// XM_00650 Nt5c3 2.32E-05 -7.20143ENSMUST00000144738 // Gm15726 // predicted gene 15726 // --- // --- Gm15726 2.20E-07 -7.24547NM_027081 // Dennd6b // DENN/MADD domain containing 6B // 15 E3|15 // 69440 /// ENSMUST Dennd6b 6.27E-06 -7.2773NR_040453 // Gm17757 // GTPase, very large interferon inducible 1 pseudogene // 7|7 // Gm17757 0.000123613 -7.3612NM_026516 // Tmem178 // transmembrane protein 178 // 17 E3|17 // 68027 /// ENSMUST00000 Tmem178 2.62E-05 -7.44068NM_001252600 // Irf7 // interferon regulatory factor 7 // 7 F5|7 // 54123 /// NM_001252 Irf7 0.000137396 -7.52212NM_001290822 // Pdpn // podoplanin // 4 E1|4 // 14726 /// NM_010329 // Pdpn // podoplan Pdpn 2.67E-09 -7.53565NM_001243039 // Gm4070 // predicted gene 4070 // 7 E3|7 // 100042856 /// NM_029000 // G Gm4070 5.83E-05 -7.54067NM_028270 // Aldh1b1 // aldehyde dehydrogenase 1 family, member B1 // 4|4 B2 // 72535 / Aldh1b1 1.91E-06 -7.64574XR_385061 // LOC102632310 // uncharacterized LOC102632310 // --- // 102632310 /// ENSMU LOC102632310 5.21E-05 -7.67563NM_022420 // Gprc5b // G protein-coupled receptor, family C, group 5, member B // 7 F3| Gprc5b 5.28E-07 -7.77616NM_001033405 // Treml2 // triggering receptor expressed on myeloid cells-like 2 // 17 C Treml2 3.52E-06 -7.80466NM_001135115 // Gm12250 // predicted gene 12250 // 11 B1.3|11 // 631323 Gm12250 0.000130021 -7.8447NM_001243039 // Gm4070 // predicted gene 4070 // 7 E3|7 // 100042856 /// NM_029000 // G Gm4070 6.88E-06 -7.9238NM_029005 // Mlkl // mixed lineage kinase domain-like // 8|8 D3 // 74568 /// XM_0065314 Mlkl 6.86E-06 -8.03043NM_001033339 // Mmp25 // matrix metallopeptidase 25 // 17 A3.3|17 // 240047 /// ENSMUST Mmp25 0.000261066 -8.12364NR_033483 // U90926 // cDNA sequence U90926 // 5 E2|5 // 57425 /// ENSMUST00000031356 / U90926 9.83E-05 -8.17275NM_001290311 // Wnk2 // WNK lysine deficient protein kinase 2 // 13 B1|13 25.07 cM // 7 Wnk2 8.54E-06 -8.17545NM_172777 // Gbp9 // guanylate-binding protein 9 // 5 E5|5 // 236573 /// XM_006534923 / Gbp9 0.000225352 -8.32867NR_003507 // Oas1b // 2-5 oligoadenylate synthetase 1B // 5 F|5 60.64 cM // 23961 /// E Oas1b 1.20E-05 -8.33593NM_172439 // Inpp5j // inositol polyphosphate 5-phosphatase J // 11 A1|11 // 170835 /// Inpp5j 4.51E-07 -8.4479NM_019440 // Irgm2 // immunity-related GTPase family M member 2 // 11 B1.3|11 // 54396 Irgm2 2.84E-05 -8.46474NM_198095 // Bst2 // bone marrow stromal cell antigen 2 // 8 B3.3|8 // 69550 /// ENSMUS Bst2 1.78E-07 -8.46968BC096584 // H2-Q5 // histocompatibility 2, Q region locus 5 // 17 B1|17 19.17 cM // 150 H2-Q5 3.04E-07 -8.48786NM_013642 // Dusp1 // dual specificity phosphatase 1 // 17 A2-C|17 13.28 cM // 19252 // Dusp1 4.32E-10 -8.70016NR_002687 // Gm5424 // argininosuccinate synthase pseudogene // 10 B4|10 // 432466 /// Gm5424 6.66E-05 -8.75188NM_021893 // Cd274 // CD274 antigen // 19|19 C2 // 60533 /// ENSMUST00000016640 // Cd27 Cd274 6.95E-06 -8.78525NM_172812 // Htr2a // 5-hydroxytryptamine (serotonin) receptor 2A // 14 D2|14 39.37 cM Htr2a 1.97E-06 -8.7979NM_001201460 // H2-Q9 // histocompatibility 2, Q region locus 9 // 17|17 // 110558 /// H2-Q9 2.44E-08 -8.84118NM_199016 // Enpp4 // ectonucleotide pyrophosphatase/phosphodiesterase 4 // 17 B3|17 // Enpp4 1.75E-05 -8.95063NM_001162938 // Pydc3 // pyrin domain containing 3 // 1 H3|1 // 100033459 /// ENSMUST00 Pydc3 0.00116798 -9.06946NR_030671 // AW011738 // expressed sequence AW011738 // 4 E2|4 // 100382 /// ENSMUST000 AW011738 9.77E-05 -9.07766NM_025465 // Tma16 // translation machinery associated 16 homolog (S. cerevisiae) // 8| Tma16 0.000279038 -9.18722NM_001143689 // H2-Q4 // histocompatibility 2, Q region locus 4 // 17 B1|17 18.65 cM // H2-Q4 8.96E-07 -9.23657NM_010751 // Mxd1 // MAX dimerization protein 1 // 6 D1|6 37.75 cM // 17119 /// ENSMUST Mxd1 8.89E-07 -9.28314--- 5.58E-05 -9.31022NM_010478 // Hspa1b // heat shock protein 1B // 17 B1|17 18.5 cM // 15511 /// ENSMUST00 Hspa1b 6.26E-05 -9.33951NM_001037713 // Xaf1 // XIAP associated factor 1 // 11 B4|11 // 327959 /// NM_001291153 Xaf1 1.09E-06 -9.46333NM_007719 // Ccr7 // chemokine (C-C motif) receptor 7 // 11 D|11 // 12775 /// XM_006532 Ccr7 0.000128619 -9.63209NM_009421 // Traf1 // TNF receptor-associated factor 1 // 2 B|2 // 22029 /// XM_0064978 Traf1 0.00133631 -9.63789NM_029509 // Gbp8 // guanylate-binding protein 8 // 5 E5|5 // 76074 /// ENSMUST00000031 Gbp8 2.17E-06 -9.75153NR_029457 // G530011O06Rik // RIKEN cDNA G530011O06 gene // X and Y|X // 654820 /// ENS G530011O06Ri 1.85E-07 -9.89493NM_001083312 // Gbp7 // guanylate binding protein 7 // 3 H1|3 // 229900 /// NM_145545 / Gbp7 0.00140936 -10.2329NM_009137 // Ccl22 // chemokine (C-C motif) ligand 22 // 8 C5|8 // 20299 /// ENSMUST000 Ccl22 0.000760111 -10.2535--- 0.000703066 -10.279BC096584 // H2-Q5 // histocompatibility 2, Q region locus 5 // 17 B1|17 19.17 cM // 150 H2-Q5 1.13E-06 -10.414BC096584 // H2-Q5 // histocompatibility 2, Q region locus 5 // 17 B1|17 19.17 cM // 150 H2-Q5 1.13E-06 -10.414BC096584 // H2-Q5 // histocompatibility 2, Q region locus 5 // 17 B1|17 19.17 cM // 150 H2-Q5 1.13E-06 -10.414NM_001293783 // Ddx60 // DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 // 8 B3.1|8 // 23431 Ddx60 2.19E-05 -10.4395NM_001039701 // Il1rn // interleukin 1 receptor antagonist // 2 A3|2 16.36 cM // 16181 Il1rn 4.58E-06 -10.7152NM_009943 // Cox6a2 // cytochrome c oxidase subunit VIa polypeptide 2 // 7 F3|7 70.04 c Cox6a2 4.16E-07 -10.9401NM_025992 // Herc6 // hect domain and RLD 6 // 6 C1|6 // 67138 /// ENSMUST00000031817 / Herc6 7.75E-06 -10.9559NM_001163014 // Gp6 // glycoprotein 6 (platelet) // 7 A1|7 // 243816 /// XM_006539909 / Gp6 1.64E-06 -11.0381NM_030710 // Slamf6 // SLAM family member 6 // 1 H3|1 79.54 cM // 30925 /// XM_00649688 Slamf6 2.92E-08 -11.046NM_145226 // Oas3 // 2-5 oligoadenylate synthetase 3 // 5 F|5 60.64 cM // 246727 /// EN Oas3 7.89E-06 -11.1677NM_001242368 // F10 // coagulation factor X // 8 A1.1|8 5.73 cM // 14058 /// NM_007972 F10 1.22E-05 -11.208NM_008768 // Orm1 // orosomucoid 1 // 4 B3|4 33.96 cM // 18405 /// ENSMUST00000030044 / Orm1 0.000386916 -11.2285NM_017370 // Hp // haptoglobin // 8 D3|8 57.11 cM // 15439 /// ENSMUST00000074898 // Hp Hp 4.08E-06 -11.5127ENSMUST00000124513 // Gm15247 // predicted gene 15247 // --- // --- /// AK019053 // Gm1 Gm15247 1.46E-07 -11.6248

NM_021394 // Zbp1 // Z-DNA binding protein 1 // 2 H3|2 // 58203 /// ENSMUST00000029018 Zbp1 2.83E-05 -11.7381NM_020498 // Ly6i // lymphocyte antigen 6 complex, locus I // 15 D3|15 // 57248 /// ENS Ly6i 1.26E-06 -11.9537NM_009369 // Tgfbi // transforming growth factor, beta induced // 13 B-C1|13 30.09 cM / Tgfbi 4.68E-11 -12.0349NR_051981 // H2-Q5 // histocompatibility 2, Q region locus 5 // 17 B1|17 19.17 cM // 15 H2-Q5 6.29E-07 -12.1669NM_183103 // Prss46 // protease, serine 46 // 9 F3|9 60.79 cM // 74306 /// ENSMUST00000 Prss46 6.39E-07 -12.2866--- 0.00203371 -12.6276NM_001164289 // Phf11c // PHD finger protein 11C // 14 C3|14 // 628705 /// ENSMUST00000 Phf11c 1.25E-05 -12.6431XR_401026 // A730011C13Rik // RIKEN cDNA A730011C13 gene // 3|3 // 319916 /// ENSMUST00 A730011C13Rik 2.88E-08 -12.6635--- 0.000129178 -12.6988NM_177363 // Tarm1 // T cell-interacting, activating receptor on myeloid cells 1 // 7 A Tarm1 0.000234213 -12.8493ENSMUST00000070435 // Fabp3-ps1 // fatty acid binding protein 3, muscle and heart, pseu Fabp3-ps1 1.38E-06 -12.8722ENSMUST00000127563 // Gm13822 // predicted gene 13822 // --- // --- Gm13822 0.000183986 -13.0386NM_001271498 // Il15ra // interleukin 15 receptor, alpha chain // 2 A1|2 8.97 cM // 161 Il15ra 6.45E-06 -13.0996ENSMUST00000057784 // Slc7a2 // solute carrier family 7 (cationic amino acid transporte Slc7a2 0.000230042 -13.3439NM_001169153 // Cd300lf // CD300 antigen like family member F // 11 E2|11 // 246746 /// Cd300lf 3.52E-08 -13.4057NM_183162 // Helz2 // helicase with zinc finger 2, transcriptional coactivator // 2 H4| Helz2 2.06E-05 -13.8937NR_027919 // Bambi-ps1 // BMP and activin membrane-bound inhibitor, pseudogene (Xenopus Bambi-ps1 4.21E-06 -14.3217NM_001162883 // Apol9a // apolipoprotein L 9a // 15 E1|15 // 223672 /// NM_173786 // Ap Apol9a 2.22E-07 -14.3949NM_013730 // Slamf1 // signaling lymphocytic activation molecule family member 1 // 1 H Slamf1 0.00320912 -14.4175NM_021443 // Ccl8 // chemokine (C-C motif) ligand 8 // 11 C|11 49.91 cM // 20307 /// EN Ccl8 4.28E-06 -14.421NM_018738 // Igtp // interferon gamma induced GTPase // 11 B1.3|11 36.01 cM // 16145 // Igtp 4.05E-05 -14.4537ENSMUST00000103463 // Ighv14-1 // immunoglobulin heavy variable 14-1 // --- // --- /// Ighv14-1 0.000126507 -14.5173NM_007981 // Acsl1 // acyl-CoA synthetase long-chain family member 1 // 8|8 B2 // 14081 Acsl1 2.13E-05 -14.8132ENSMUST00000122664 // n-R5s164 // nuclear encoded rRNA 5S 164 // --- // --- n-R5s164 5.22E-05 -14.8395NM_008332 // Ifit2 // interferon-induced protein with tetratricopeptide repeats 2 // 19 Ifit2 0.000556178 -14.9426NM_001081746 // Gm7609 // predicted pseudogene 7609 // 1 C5|1 // 665378 /// ENSMUST0000 Gm7609 8.95E-05 -14.9947NM_001198560 // H2-Q7 // histocompatibility 2, Q region locus 7 // 17 B1|17 18.67 cM // H2-Q7 1.83E-05 -15.2173NM_007646 // Cd38 // CD38 antigen // 5 B3|5 23.85 cM // 12494 /// ENSMUST00000030964 // Cd38 0.00178186 -15.3858ENSMUST00000031264 // Plac8 // placenta-specific 8 // 5 E3|5 48.49 cM // 231507 /// ENS Plac8 1.15E-07 -15.4398ENSMUST00000174699 // H2-Q6 // histocompatibility 2, Q region locus 6 // 17 B1|17 18.66 H2-Q6 5.99E-09 -15.5953--- 0.000302186 -15.6318XM_006498216 // Ptges // prostaglandin E synthase // 2 B|2 21.75 cM // 64292 /// NM_022 Ptges 0.000139599 -16.0282NM_199015 // Phf11d // PHD finger protein 11D // 14 C3|14 31.48 cM // 219132 /// XM_006 Phf11d 8.01E-06 -16.2404NM_001164329 // Gm6904 // predicted gene 6904 // 14 C3|14 // 628693 /// ENSMUST00000168 Gm6904 8.62E-07 -16.6213NM_015783 // Isg15 // ISG15 ubiquitin-like modifier // 4 E2|4 // 100038882 /// ENSMUST0 Isg15 0.000144816 -16.8385NM_011331 // Ccl12 // chemokine (C-C motif) ligand 12 // 11 C|11 49.9 cM // 20293 /// E Ccl12 0.0008682 -16.9561NR_102366 // AW112010 // expressed sequence AW112010 // 19 A|19 // 107350 /// ENSMUST00 AW112010 0.00174339 -16.9819NM_001025606 // Tmem171 // transmembrane protein 171 // 13 D1|13 // 380863 /// ENSMUST0 Tmem171 9.08E-07 -17.2789NM_001164327 // Phf11b // PHD finger protein 11B // 14 C3|14 // 236451 /// ENSMUST00000 Phf11b 2.92E-05 -17.4831NM_001291220 // Isg20 // interferon-stimulated protein // 7 D3|7 // 57444 /// NM_001113 Isg20 2.91E-05 -17.8265XR_378392 // Trim30c // tripartite motif-containing 30C // 7 E3|7 // 434219 /// ENSMUST Trim30c 0.000321372 -18.0485NM_008491 // Lcn2 // lipocalin 2 // 2 A3|2 22.09 cM // 16819 /// ENSMUST00000050785 // Lcn2 5.50E-05 -18.1517XM_006527251 // Ms4a4c // membrane-spanning 4-domains, subfamily A, member 4C // 19 A|1 Ms4a4c 7.55E-05 -18.3302NM_032541 // Hamp // hepcidin antimicrobial peptide // 7 B1|7 19.27 cM // 84506 /// ENS Hamp 0.000392925 -18.6505NM_010260 // Gbp2 // guanylate binding protein 2 // 3 H1|3 66.69 cM // 14469 /// ENSMUS Gbp2 0.000376301 -18.826NM_027890 // Susd2 // sushi domain containing 2 // 10|10 B5.3 // 71733 /// ENSMUST00000 Susd2 2.51E-08 -18.8352--- 1.77E-06 -18.8829XR_397994 // BC023105 // cDNA sequence BC023105 // 18 D3|18 // 667597 /// ENSMUST000000 BC023105 1.01E-05 -19.4826NM_001013832 // Gpr31b // G protein-coupled receptor 31, D17Leh66b region // 17 A1|17 8 Gpr31b 2.58E-05 -19.7847NM_010479 // Hspa1a // heat shock protein 1A // 17 B1|17 18.51 cM // 193740 /// ENSMUST Hspa1a 1.63E-06 -20.2312NM_001164059 // Sell // selectin, lymphocyte // 1 H2.2|1 71.37 cM // 20343 /// NM_01134 Sell 3.50E-08 -20.3183NM_172621 // Clic5 // chloride intracellular channel 5 // 17|17 C // 224796 /// XM_0065 Clic5 2.60E-06 -20.6164NM_011909 // Usp18 // ubiquitin specific peptidase 18 // 6 F|6 57.17 cM // 24110 /// EN Usp18 1.49E-05 -21.2011NM_008392 // Irg1 // immunoresponsive gene 1 // 14 E2.3|14 51.67 cM // 16365 /// XM_006 Irg1 0.0042112 -21.4099NM_001099217 // Ly6c2 // lymphocyte antigen 6 complex, locus C2 // 15 D3|15 // 10004154 Ly6c2 2.15E-07 -21.6159NR_027852 // Cd40 // CD40 antigen // 2 H3|2 85.38 cM // 21939 /// ENSMUST00000017799 // Cd40 0.00375845 -21.756NM_144548 // Il23r // interleukin 23 receptor // 6 C1|6 // 209590 /// ENSMUST0000011836 Il23r 1.46E-06 -22.1005NM_009425 // Tnfsf10 // tumor necrosis factor (ligand) superfamily, member 10 // 3 A3|3 Tnfsf10 0.00107093 -22.3176NM_001081746 // Gm7609 // predicted pseudogene 7609 // 1 C5|1 // 665378 /// NM_033616 / Gm7609 1.32E-06 -22.7148NM_001037925 // BC147527 // cDNA sequence BC147527 // 13|13 // 625360 /// XM_006517732 BC147527 2.86E-06 -22.8038NM_029612 // Slamf9 // SLAM family member 9 // 1 H3|1 // 98365 /// XM_006497067 // Slam Slamf9 1.18E-06 -23.4245NM_001198560 // H2-Q7 // histocompatibility 2, Q region locus 7 // 17 B1|17 18.67 cM // H2-Q7 2.04E-08 -23.8557ENSMUST00000093501 // A530040E14Rik // RIKEN cDNA A530040E14 gene // 1 C5|1 // 621875 / A530040E14Rik 0.00030879 -24.2122NM_001045543 // Heatr9 // HEAT repeat containing 9 // 11 C|11 // 629303 /// XM_00653390 Heatr9 2.44E-06 -24.4061NM_001177471 // Gm15056 // predicted gene 15056 // 8 A2|8 // 100504014 /// ENSMUST00000 Gm15056 5.18E-06 -24.7977NM_008331 // Ifit1 // interferon-induced protein with tetratricopeptide repeats 1 // 19 Ifit1 0.000411406 -26.1016NM_001081746 // Gm7609 // predicted pseudogene 7609 // 1 C5|1 // 665378 /// NM_033616 / Gm7609 1.28E-07 -27.0713NM_001081746 // Gm7609 // predicted pseudogene 7609 // 1 C5|1 // 665378 /// NM_033616 / Gm7609 3.90E-07 -27.755NM_001081746 // Gm7609 // predicted pseudogene 7609 // 1 C5|1 // 665378 /// NM_033616 / Gm7609 3.90E-07 -27.755NM_001168660 // Apol9b // apolipoprotein L 9b // 15 E1|15 // 71898 /// NM_173743 // Apo Apol9b 8.37E-06 -27.8129NM_001033767 // Gm4951 // predicted gene 4951 // 18 D3|18 // 240327 /// ENSMUST00000031 Gm4951 0.000191468 -28.0123NR_029565 // Mir155 // microRNA 155 // 16|16 // 387173 /// ENSMUST00000083463 // Mir155 Mir155 0.00403794 -28.4615NM_010612 // Kdr // kinase insert domain protein receptor // 5 C3.3|5 40.23 cM // 16542 Kdr 6.78E-07 -28.6334NM_001289492 // Gbp3 // guanylate binding protein 3 // 3 H1|3 // 55932 /// NM_001289493 Gbp3 0.000701966 -29.3378NM_013606 // Mx2 // myxovirus (influenza virus) resistance 2 // 16 C4|16 57.51 cM // 17 Mx2 5.77E-05 -31.2033NM_175026 // Pyhin1 // pyrin and HIN domain family, member 1 // 1 H3|1 // 236312 /// EN Pyhin1 8.94E-05 -31.2319NM_020557 // Cmpk2 // cytidine monophosphate (UMP-CMP) kinase 2, mitochondrial // 12 A2 Cmpk2 0.000456953 -31.3415NM_153564 // Gbp5 // guanylate binding protein 5 // 3 H1|3 // 229898 /// ENSMUST0000009 Gbp5 0.00366419 -31.4906NM_008204 // H2-M2 // histocompatibility 2, M region locus 2 // 17 B1|17 19.16 cM // 14 H2-M2 9.61E-06 6.23E-07NM_001083322 // Klrk1 // killer cell lectin-like receptor subfamily K, member 1 // 6 F3 Klrk1 3.02E-05 -34.5985NM_001177349 // Pydc4 // pyrin domain containing 4 // 1 H3|1 // 623121 /// NM_001177350 Pydc4 9.90E-07 -34.7497NM_172603 // Phf11a // PHD finger protein 11A // 14 C3|14 // 219131 /// ENSMUST00000062 Phf11a 4.86E-05 -36.4006NM_001271416 // Ly6a // lymphocyte antigen 6 complex, locus A // 15 D3|15 34.29 cM // 1 Ly6a 6.05E-10 -37.3877NM_145209 // Oasl1 // 2-5 oligoadenylate synthetase-like 1 // 5 F|5 // 231655 /// ENSMU Oasl1 6.01E-05 -38.3046NM_011246 // Rasgrp1 // RAS guanyl releasing protein 1 // 2 E5|2 59.19 cM // 19419 /// Rasgrp1 0.00022037 -40.075NM_010846 // Mx1 // myxovirus (influenza virus) resistance 1 // 16 C4|16 57.46 cM // 17 Mx1 0.000196796 -40.6093NM_001256005 // Gbp4 // guanylate binding protein 4 // 5 E5|5 50.68 cM // 17472 /// ENS Gbp4 0.000214556 -43.9247ENSMUST00000090406 // BC094916 // cDNA sequence BC094916 // 1 H3|1 // 545384 /// ENSMUS BC094916 4.77E-05 -52.3816NM_001146275 // Iigp1 // interferon inducible GTPase 1 // 18 D3|18 // 60440 /// ENSMUST Iigp1 0.000263071 -52.5602ENSMUST00000137792 // Rsad2 // radical S-adenosyl methionine domain containing 2 // 12| Rsad2 0.000113028 -53.0382ENSMUST00000047498 // AA467197 // expressed sequence AA467197 // 2 E5|2 // 433470 /// N AA467197 8.30E-05 -56.8339NM_001039646 // Gbp10 // guanylate-binding protein 10 // 5 E5|5 // 626578 /// ENSMUST00 Gbp10 6.99E-05 -58.3462ENSMUST00000128411 // Tgtp2 // T cell specific GTPase 2 // 11 B1.2|11 // 100039796 /// Tgtp2 0.000266187 -71.187NM_172648 // Ifi205 // interferon activated gene 205 // 1 H3|1 80.83 cM // 226695 /// E Ifi205 0.00109062 -71.4535XM_003945749 // LOC630751 // interferon-inducible GTPase 1-like // --- // 630751 /// XR LOC630751 3.92E-05 -77.0482

NM_001167828 // Trim30d // tripartite motif-containing 30D // 7 E3|7 // 209387 /// NM_1 Trim30d 0.000185465 -80.507NM_008599 // Cxcl9 // chemokine (C-X-C motif) ligand 9 // 5 E2|5 46.51 cM // 17329 /// Cxcl9 0.000569276 -83.4258NM_001110517 // Gm14446 // predicted gene 14446 // 19 C1|19 // 667373 Gm14446 3.38E-07 -83.8296NM_021274 // Cxcl10 // chemokine (C-X-C motif) ligand 10 // 5 E2|5 46.57 cM // 15945 // Cxcl10 0.00116546 -96.7691NM_001142706 // Cfb // complement factor B // 17 B1|17 18.41 cM // 14962 /// NM_008198 Cfb 0.000452834 -103.398NM_009977 // Cst7 // cystatin F (leukocystatin) // 2|2 G1-G3 // 13011 /// ENSMUST000000 Cst7 9.03E-06 -110.042NM_001039647 // Gbp11 // guanylate binding protein 11 // 5 E5|5 // 634650 /// ENSMUST00 Gbp11 4.41E-05 -112.616NM_010927 // Nos2 // nitric oxide synthase 2, inducible // 11 B5|11 46.74 cM // 18126 / Nos2 0.000344268 -169.378NM_011410 // Slfn4 // schlafen 4 // 11 C|11 // 20558 /// ENSMUST00000000208 // Slfn4 // Slfn4 9.12E-05 -187.205NM_011407 // Slfn1 // schlafen 1 // 11 C|11 50.3 cM // 20555 /// ENSMUST00000037994 // Slfn1 2.39E-05 -237.965NM_019494 // Cxcl11 // chemokine (C-X-C motif) ligand 11 // 5|5 E3 // 56066 /// NR_0381 Cxcl11 0.00134012 -258.558

253

APPENDIX II: FhHDM-1 inhibits cytokine expression in response to

LPS treated BMDMs isolated from C57BL6 mice

U ntre a te d L P S L P S + F hH D M -10

2 0 0

4 0 0

6 0 0

8 0 0

TN

F (

pg

/mL

)

****

# # # #


2 0 0

4 0 0

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CC

L2

(p

g/m

L)

****

# # # #


2 0 0

4 0 0

6 0 0

8 0 0

1 0 0 0

1 2 0 0

1 4 0 0

1 6 0 0

IL-6

(pg

/mL

)

****

# # # #

APPENDIX II: FhHDM-1 inhibits LPS-induced inflammatory mediator release in BMDMs

isolated from C57BL6 mice. Bars represent mean ± SEM from six experiments. ****P < .0001

vs untreated cells. #### P < .0001 vs cells stimulated with LPS only.

255

APPENDIX III: FhHDM1 inhibits airway neutrophilic inflammation in

LPS treated mice

S a line

L P S

L P S & F

h H D M-1

0 .0

0 .5

1 .0

1 .5

2 .0

2 .5

**

S a line

L P S

L P S & F

h H D M-1

0 .0

0 .5

1 .0

1 .5

2 .0

2 .5

**

PBS LPS LPS+ FhHDM-1

Neu

troph

ils x

106 /m

LTo

tal C

ells

x10

6 /mL

2.0

0

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1.0

0.5

APPENDIX III: FhHDM-1 inhibits LPS-induced increases in total cellsand neutrophils in mice challenged with an intratracheal deliveryof LPS. Bars represent mean ± SEM. *P < .05, **P < .01, and ***P <.001 vs mice treated with HDM or LPS only. N= 6 mice per group.

Innate Immune Mechanisms of Chronic Airways …...Innate Immune Mechanisms of Chronic Airways Disease A thesis submitted for the degree of Doctor of Philosophy Venkata Sita Rama Raju

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