UvA-DARE (Digital Academic Repository) The Pitx3-deficient ... · 12. Amendt BA, Sutherland LB, Semina EV, Russo AF: The molecular basis of Rieger syndrome. analysis of Pitx2 homeodomain

UvA-DARE is a service provided by the library of the University of Amsterdam (http://dare.uva.nl)

UvA-DARE (Digital Academic Repository)

The Pitx3-deficient aphakia mouse: a naturally occurring mouse model of dopaminedeficiency

van den Munckhof, P.

Link to publication

Citation for published version (APA):van den Munckhof, P. (2011). The Pitx3-deficient aphakia mouse: a naturally occurring mouse model ofdopamine deficiency.

General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s),other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons).

Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, statingyour reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Askthe Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam,The Netherlands. You will be contacted as soon as possible.

Download date: 17 Oct 2020

References

135

References

1. Acampora D, Mazan S, Lallemand Y, Avantaggiato V, Maury M, Simeone A, Brûlet P: Forebrain and

midbrain regions are deleted in Otx2-/- mutants due to a defective anterior neuroectoderm specification

during gastrulation. Development 121:3279-3290, 1995.

2. Agamanolis DP, Greenstein JI: Ataxia-telangiectasia. Report of a vase with Ley bodies and vascular

abnormalities within cerebral tissue. J Neuropathol Exp Neurol 38:475-489, 1979.

3. Agarwala S, Sanders TA, Ragsdale CW: Sonic Hedgehog control of size and shape in midbrain pattern

formation. Science 291:2147-2150, 2001.

4. Airaksinen MS, Thoenen H, Meyer M: Vulnerability of midbrain dopaminergic neurons in calbindin-D-28k-

deficient mice: Lack of evidence for a neuroprotective role of endogenous calbindin in MPTP-treated and

weaver mice. European Journal of Neuroscience 9: 120-127, 1997.

5. Alam M, Smidt WJ: L-DOPA reverses the hypokinetic behaviour and rigidity in rotenone-treated rats.

Behav Brain Res 153:439-446, 2004.

6. Alberi L, Sgado P, Simon HH: Engrailed genes are cell-independently required to prevent apoptosis in

mesencephalic dopaminergic neurons. Development 131: 3229-3236, 2004.

7. Altman J, Bayer SA: Development of the brain stem in the rat. V. Thymidine-radiographic study of the time

of origin of neurons in the midbrain tegmentum. J Comp Neurol 198:677-716, 1981.

8. Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST:

a new generation of protein database search programs. Nucleic Acids Res 25:3389-3402, 1997.

9. Altschul SF, Wootton JC, Gertz EM, Agarwala R, Morgulis A, Schäffer AA, Y YK: Protein database searches

using compositionally adjusted substitution matrices. FEBS J 272:5101-5109, 2005.

10. Alvarez V, Corao AI, Sánchez-Ferrero E, De Mena L, Alonso-Montes C, Huerta C, Blázquez M, Ribacoba R,

Guisasola LM, Salvador C, García-Castro M, Coto E: Mitochondrial transcription factor A (TFAM) gene

variation in Parkinson’s disease. Neurosci Lett 432:79-82, 2008.

11. Alvarez-Fischer D, Henze C, Strenzke C, Westrich J, Ferger B, Höglinger GU, Oertel WH, Hartmann A:

Characterization of the striatal 6-OHDA model of Parkinson’s disease in wild type and α-synuclein-deleted

mice. Exp Neurol 210:182-193, 2008.

12. Amendt BA, Sutherland LB, Semina EV, Russo AF: The molecular basis of Rieger syndrome. analysis of Pitx2

homeodomain protein activities. J Biol Chem 273:20066-20072, 1998.

13. Ang SL, Jin O, Rhinn M, Daigle N, Stevenson L, Rossant J: A targeted mouse Otx2 mutation leads to severe

defects in gastrulation and formation of axial mesoderm and to deletion of rostral brain. Development

122:243-252, 1996.

14. Arai N, Misugi K, Goshima Y, Misu Y: Evaluation of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine (MPTP)-

treated C57 black mouse model for parkinsonism. Brain Res 515:57-63, 1990.

15. Arakawa H, Nakamura T, Zhadanov AB, Fidanza V, Yano T, Bullrich F, Shimizu M, Blechman J, Mazo A,

Canaani E, Croce CM: Identification and characterization of the ARP1 gene, a target for the human acute

leukemia ALL1 gene. Proc Natl Acad Sci USA 95:4573-4578, 1998.

16. Asano M, Gruss P: Pax-5 is expressed at the midbrain-hindbrain boundary during mouse development.

Mech Dev 39:29-39, 1992.

17. Asbreuk CHJ, Vogelaar CF, Hellemons A, Smidt MP, Burbach JPH: CNS expression pattern of Lmx1b and

coexpression with Ptx genes suggest functional cooperativity in the development of forebrain motor

control systems. Mol Cell Neurosci 21: 410-420, 2002.

18. Bäckman C, Perlmann T, Wallén Am Hoffer BJ, Morales M: A selective group of dopaminergic neurons

express Nurr1 in the adult mouse brain. Brain Res 851:125-132, 1999.

19. Baffi JS, Palkovits M, Castillo SO, Mezey E, Nikodem VM: Differential expression of tyrosine hydroxylase in

catecholaminergic neurons of neonatal wildt-type and Nurr1-deficient mice. Neuroscience 93:631-642,

1999.

Appendices

136

20. Baik JH, Picetti R, Dalardi A, Thirlet G, Dierich A, Depaulis A, Le Meur M, Borrelli E: Parkinsonian-like

locomotor impairment in mice lacking dopamine D2 receptors. Nature 377:424-428, 1995.

21. Bandmann O, Davis MB, Marsden CD, Wood NW: The human homologue of the weaver mouse gene in

familial and sporadic Parkinson’s disease. Neuroscience 72:877-879, 1996.

22. Bannon MJ, Pruetz B, Manning-Bog AB, Whitty CJ, Michelhaugh SK, Sacchetti P, Granneman JG, Mash DC,

Schmidt CJ: Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine

abusers. Proc Natl Acad Sci USA 99:6382-6385, 2002.

23. Barde YA: Trophic factors and neuronal survival. Neuron 2:1525-1534, 1989.

24. Barlow C, Hirotsune S, Paylor R, Liyanage M, Eckhaus M, Collins F, Shiloh Y, Crawley JN, Ried T, Tagle D,

Wynshaw-Boris A: Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell 86:159-171, 1996.

25. Bayer SA, Wills KV, Triarhou LC, Verina T, Thomas JD, Ghetti B: Selective vulnerability of late-generated

dopaminergic neurons of the substantia nigra in weaver mutant mice. Proc Natl Acad Sci USA 92:9137-

9140, 1995.

26. Beach TG, Adler CH, Lue L, Sue LI, Bachalakuri J, Henry-Watson J, Sasse J, Boyer S, Shirohi S, Brooks R,

Eschbacher J, White CL 3rd

, Akiyama H, Caviness J, Shill HA, Connor DJ, Sabbagh MN, Walker DG; Arizona

Parkinson’s Disease Consortium: Unified staging system for Lewy body disorders: correlation with

nigrostriatal degeneration, cognitive impairment and motor dysfunction. Acta Neuropathol 117:613-634,

2009.

27. Beaudry G, Langlois MC, Weppe I, Rouillard C, Levesque D: Contrasting patterns and cellular specificity of

transcriptional regulation of the nuclear receptor nerve growth factor-inducible B by haloperidol and

clozapine in the rat forebrain. J Neurochem 75:1694-1702, 2000.

28. Beckstead RM, Domesick VB, Nauta WJH: Efferent connections of the substantia nigra and ventral

tegmental area in the rat. Brain Res 175:191-217, 1979.

29. Beddington and Robertson: Anterior patterning in mouse. Trends Genet 14:277-284, 1998.

30. Beeler JA, Cao ZF, Kheirbek MA, Zhuang X: Loss of cocaine locomotor response in Pitx3-deficient mice

lacking a nigrostriatal pathway. Neuropsychopharmacology 34:1149-1161, 2009.

31. Berendse HW, Galis-de Graaf Y, Groenewegen HJ: Topographical organization and relationship with

ventral striatal compartments of prefrontal corticostriatal projections in the rat. J Comp Neurol 316:314-

347, 1992.

32. Berendse HW and Groenewegen HJ: Organization of the thalamocortical projections in the rat, with

special emphasis on the ventral striatum. J Comp Neurol 299:187-228, 1990.

33. Berendse HW, Groenewegen HJ, Lohman AH: Compartmental distribution of ventral striatal neurons

projecting to the mesencephalon in the rat. J Neurosci 12:2079-2103, 1992.

34. Bergman O, Hakansson A, Westberg L, Nordenstrom K, Carmine BA, Sydow O, Olson L, Holmberg B,

Eriksson E, Nissbrandt H: PITX3 polymorphism is associated with early onset Parkinson's disease.

Neurobiol Aging, 31:114-117, 2010.

35. Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F: Brain dopamine and the

syndromes of Parkinson and Huntington: clinical, morphological and neurochemical correlations. J Neurol

Scie 20:415-455, 1973.

36. Berry V, Yang Z, Addison PK, Francis PJ, Ionides A, Karan G, Jiang L, Lin W, Hu J, Yang R, Moore A, Zhang K,

Bhattacharya SS: Recurrent 17 bp duplication in PITX3 is primarly associated with posterior polar cataract

(CPP4). J Med Genet 41:e109, 2004.

37. Besson MJ, Graybiel AM, Quinn B: Co-expression of neuropeptides in the cat’s striatum: an

immunohistochemical study of substance P, dynorphin B and enkephalin. Neuroscience 39:33-58, 1990.

38. Bethlem J, Den Hartog Jager WA: The incidence and characteristics of Lewy bodies in idiopathic paralysis

agitans (Parkinson’s disease). J Neurol Neurosurg Psychiatry 23:74-80, 1960.

39. Birkmayer W, Hornykiewicz: The L-3,4-dioxyphenylalanine (DOPA)-effect in Parkinson-akinesia. Wien Klin

Wochenschr 73:787-788, 1961.

References

137

40. Björklund A, Lindvall O: Dopamine in dendrites of substantia nigra neurons: suggestions for a role in

dendritic terminals. Brain Res 83: 531-537, 1975.

41. Björklund A, Lindvall O: Dopamine-containing system in the CNS. In: Björklund A, Hökfelt T (eds) Handbook

of Chemical Neuroanatomy: Classical Neurotransmitters in the CNS Volume 2, 55-122, Elsevier,

Amsterdam, 1984.

42. Blume SR, Cass DK, Tseng KY: Stepping test in mice: a reliable approach in determining forelimb akinesia in

MPTP-induced parkinsonism. Exp Neurol 219:208-211, 2009.

43. Boder E, Sedgwick RP: Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia,

oculocutaneous telangiectasia and frequent pulmonary infection. Pediatrics 21:526-554, 1958.

44. Boja JW, Cadet JL, Kopajtic TA, Lever J, Seltzman HH, Wyrick CD, Lewin AH, Abraham P, Carroll FI: Selective

labelling of the dopamine transporter by high affinity ligand 3β-(4-[125

]iodophenyl) tropane-2 β-carboxylic

acid isopropyl ester. Mol Pharmacol 47:779-786, 1995.

45. Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P,

Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink

P: Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science

299:256-259, 2003.

46. Bonifati V, Rohé CF, Breedveld GJ, Fabrizio E, De Mari M, Tassorelli C, Tavella A, Marconi R, Nicholl DJ,

Chien HF, Fincati E, Abbruzzese G, Marini P, De Gaetano A, Horstink MW, Maat-Kievit JA, Sampaio C,

Antonini A, Stocchi F, Montagna P, Toni V, Guidi M, Dalla Libera A, Tinazzi M, De Pandis F, Fabbrini G,

Goldwurm S, de Klein A, Barbosa E, Lopiano L, Martignoni E, Lamberti P, Vanacore N, Meco G, Oostra BA:

Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes.

Neurology 65:87-95, 2005.

47. Bordet R, Ridray S, Carboni S, Diaz J, Sokoloff P, Schwartz JC: Induction of dopamine D3 receptor

expression as a mechanism of behavioural sensitization to levodopa. Proc Natl, Acad Sci USA 94:3363-

3367, 1997.

48. Bower JH, Maraganore DM, McDonnell SK, Rocca WA: Incidence and distribution of parkinsonism in

Olmsted Country, Minnesota, 1976-1990. Neurology 52:1214-1220, 1999.

49. Braak H, Braak E, Yilmazer D, Schultz C, de Vos RA, Jansen EN: Nigral and extranigral pathology in

Parkinson’s disease. J Neural Transm Suppl 46:15-31, 1995.

50. Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E: Staging of brain pathology related to

sporadic Parkinson’s disease. Neurobiol Aging 24:197-211, 2003.

51. Briscoe J and Ericson J: Specification of neuronal fates in the ventral neural tube. Curr Opin Neurobiol

11:43-49, 2001.

52. Briscoe J, Sussel L, Serup P, Hartigan-OÇonnor D, Jessel TM, Rubenstein JL, Ericson J: Homeobox gene

Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. Nature 398:622-627,

1999.

53. Briscoe J, Pierani A, Jessell TM, Ericson: A homeodomain protein code specifies progenitor cell identity and

neuronal fate in the ventral neural tube. Cell 101:435-445, 2000.

54. Buervenich S, Carmine A, Arvidsson M, Xiang F, Zhang Z, Sydow O, Jönsson EG, Sedvall GC, Leonard S, Ross

RG, Freedman R, Chowdari KV, Nimgaonkar VL, Perlmann T, Anvret M, Olson L: NURR1 mutations in cases

of schizophrenia and manic-depressive disorder. Am J Med Genet 96:808-813, 2000.

55. Burris KD, Filtz TM, Chumpradit S, Kung MP, Foulon C, Hensler JG, Kung HF, Molinoff PB: Characterization

of [125

](R)-trans-7-hydroxy-2-[N-propyl-N(3’-iodo-2’-propenyl)amino] tetralin binding to dopamine D3

receptors in rat olfactory tubercle. J Pharmacol Exp Ther 268:935-942, 1994.

56. Caboche J, Rogard M, Besson MJ: Comparative development of D1-dopamine and mu opiate receptors in

normal and in 6-hydroxydopamine-lesioned neonatal rat striatum: dopaminergic fibers regulate mu but

not D1 receptor distribution. Brain Res Dev Brain Res 58:111-122, 1991.

Appendices

138

57. Calof AL: Intrinsic and extrinsic factors regulating vertebrate neurogenesis. Curr Opin Neurobiol 5:19-27,

1995.

58. Calon F, Hadj Tahar A, Blanchet PJ, Morissette M, Grondin R, Goulet M, Doucet JP, Robertson GS, Nestler E,

Di Paolo T, Bédard PJ: Dopamine-receptor stimulation: biobehavioral and biochemical consequences.

Trends Neuroscie 23:S92-S100, 2000.

59. Cannon JR, Tapias V, Na HM, Honick AS, Drolet RE, Greenamyre JT: A highly reproducible rotenone model

of Parkinson’s disease. Neurobiol Dis 34:279-290, 2009.

60. Castillo SO, Baffi JS, Palkovits M, Goldstein DS, Kopin IJ, Witta J, Magnuson MA, Nikodem VM: Dopamine

biosynthesis is selectively abolished in substantia nigra/ventral tegmental area but not in hypothalamic

neurons in mice with targeted disruption of the Nurr1 gene. Mol Cell Neurosci 11:36-46, 1998.

61. Castro DS, Hermanson E, Jospeh B, Wallén A, Aarnisalo P, Heller A, Perlmann T: Induction of cell cycle

arrest and morphological differentiation by Nurr1 and retinoids in dopamine MN9D cells. J Biol Chem

276:43277-43284, 2001.

62. Caudle WM, Richardson JR, Wang MZ, Taylor TN, Guillot TS, McCormack AL, Colebrooke RE, Di Monte DA,

Emson PC, Miller GW: Reduced vesicular storage of dopamine causes progressive nigrostriatal

neurodegeneration. J Neurosci 27:8138-8148, 2007.

63. Cazorla P, Smidt MP, O’Malley KL, Burbach JP: A response element for the homeodomain transcription

factor Ptx3 in the tyrosine hydroxylase gene promoter. J Neurochem 74:1829-37, 2000.

64. Cenci MA, Lee CS, Björklund A: L-DOPA-induced dyskinesias in the rat is associated with striatal

overexpression of pro-dynorphin- and glutamic acid decarboxylase mRNA. Eur J Neurosci 10:2694-2706,

1998.

65. Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, Tkatch T, Meredith GE, Surmeier DJ: 'Rejuvenation'

protects neurons in mouse models of Parkinson's disease. Nature 447: 1081-1085, 2007.

66. Chen H, Lun Y, Ovchinnikov D, Kokubo H, Oberg KC, Pepicelli CV, Gan L, Lee B, Johnson RL: Limb and kidney

defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome. Nat

Genet 19:51-55, 1998.

67. Chen YH, Tsai MT, Shaw CK, Chen CH: Mutation analysis of the human NR4A2 gene, an essential gene for

midbrain dopaminergic neurogenesis, in schizophrenic patients. Am J Med Genet 105:753-757, 2001.

68. Chiang C, Litingtung Y, Lee E, Young KE, Corden JL, Westphal H, Beachy PA: Cyclopia and defective axial

patterning in mice lacking Sonic hedgehog gene function. Nature 383:407-413, 1996.

69. Chinaglia G. Alvarez FJ, Probst A, Palacios JM: Mesostriatal and mesolimbic dopamine uptake sites are

reduced in Parkinson’s disease and progressive supranuclear palsy: a quantative autoradiographic study

using [3H]mazindol. Neuroscience 49:317-327, 1992.

70. Colebrooke RE, Chan PM, Lynch PJ, Mooslehner K, Emson PC: Differential gene expression in the striatum

of mice with very low expression of the vesicular monoamine transporter type 2 gene. Brain Res 1152:10-

16, 2007.

71. Colebrooke RE, Humby T, Lynch PJ, McGowan DP, Xia J, Emson PC: Age-related decline in striatal

dopamine content and motor performance occurs in the absence of nigral cell loss in a genetic mouse

model of Parkinson’s disease. Eur J Neurosci 24:2622-2630, 2006.

72. Cotzias GC, Van Woert MH, Schiffer LM: Aromatic amino acids and modification of parkinsonism. N Engl J

Med 276:374-379, 1967.

73. Cowan WM, Fawcett JW, O’Leary DD, Stanfield BB: Regressive events in neurogenesis. Science 225:1258-

1265, 1984.

74. Coyle JT: Biochemical aspects of neurotransmission in the developing brain. Int Rev Neurobiol 20:65-103,

1977.

75. Crossley PH, Martinez S, Martin GR: Midbrain development induced by FGF8 in the chick embryo. Nature

380:66-68, 1996.

References

139

76. Damier P, Hirsch EC, Agid Y, Graybiel AM: The substantia nigra of the human brain. II. Patterns of loss of

dopamine-contaning neurons in Parkinson’s disease. Brain 122:1437-1448, 1999.

77. Date I, Felten DL, Felten SY: Long-term effect of MPTP in the mouse brain in relation to aging:

neurochemical and immunocytochemical analysis. Brain Res 519:266-276, 1990.

78. Davis CA, Joyner AL: Expression patterns of the homeo box-containing genes En-1 and En-2 and the proto-

oncogene int-1 diverge during mouse development. Genes Dev 2:1736-1744, 1988.

79. Davis GC, Williams AC, Markey SP, Ebert MH, Caine ED, Reichert CM, Kopin IJ: Chronic parkinsonism

secondary to intravenous injection of meperidine analogues. Psychiatry Res 1:249-54, 1979.

80. Dawson T, Mandir A, Lee M: Animal models of PD: pieces of the same puzzle? Neuron 35:219-222, 2002.

81. De León GA, Grover WD, Huff DS: Neuropathologic changes in ataxia-telangiectasia. Neurology 26:947-951,

1976.

82. De Rijk MC, Launer LJ, Berger K, Breteler MM, Dartigues JF, Baldereschi M, Fratiglioni L, Lobo A, Martinez-

Lage J, Trenkwalder C, Hofman A: Prevalence of Parkinson’s disease in Europe: A collaborative study of

population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 54:S21-S23, 2000.

83. De Rover M, Lodder JC, Smidt MP, Brussaard AB: Pitx3 deficiency in mice affects cholinergic modulation of

GABAergic synapses in the nucleus accumbens. J Neurophysiol 96:2034-2041, 2006.

84. Devinsky O: Neuroanatomy of Gilles de la Tourette’s syndrome. Possible midbrain involvement. Arch

Neurol 40:508-514, 1983.

85. Di Porzio U, Zuddas A, Cosenza-Murphy DB, Barker JL: Early appearance of tyrosine hydroxylase

immunoreactive cells in the mesencephalon of mouse embryos. Int J Dev Neurosci 8:523-532, 1990.

86. Dickinson SD, Sabeti J, Larson GA, Giardina K, Rubinstein M, Kelly MA, GRandy DK, Low MJ, Gerhardt GA,

Zahniser NR: Dopamine D2 receptor-deficient mice exhibit decreased dopamine transporter function but

no changes in dopamine release in dorsal striatum. J Neurochem 72:148-156, 1999.

87. DiFiglia M, Pasik P. Pasik T: A Golgi study of neuronal types in the neostriatum of monkeys. Brain Res

114:245-256, 1976.

88. Ding Y, Restrepo J, Won L, Hwang DY, Kim KS, Kang UJ: Chronic 3,4-dihydroxyphenylalanine treatment

induces dyskinesia in aphakia mice, a novel genetic model of Parkinson’s disease. Neurobiol Dis 27:11-23,

2007.

89. Drago J, Gerfen CR, Lachowicz JE, Steiner H, Hollon TR, Love PE, Ooi GT, Grinberg A, Lee EJ, Huang SP,

Bartlett PF, Jose PA, Sibley DR, Westphall H: Altered striatal function in a mutant mouse lacking D1A

dopamine receptors. Proc Natl Acad Sci USA 91:12564-12568, 1994.

90. Drago J, Padungchaichot P, Accili D, Fuch S: Dopamine receptors and dopamine transporter in brain

function and addictive behaviors: insights from targeted mouse mutants. Dev Neurosci 20:188-203, 1998.

91. Drouin J, Lamolet B, Lamonerie T, Lanctôt, C, Tremblay JJ: The PTX family of homeodomain transcription

factors during pituitary development. Mol Cell Endocrinol 140:31-36, 1998.

92. Duester G: Families of retinoid dehydrogenases regulating vitamin A function: production of visual

pigment and retinoic acid. Eur J Biochem 267:4315-4324, 2000.

93. Eells JB, Rives JE, Yeung SK, Nikodem VM: In vitro regulated expression of tyrosine hydroxylase in ventral

midbrain neurons from Nurr1-null mouse pups. J Neuroscie Res 64:322-330, 2001.

94. Egan MF, Weinberger DR: Neurobiology of schizophrenia. Curr Opin Neurobiol 7:701-707, 1987.

95. Eilam R, Peter Y, Elson A, Rotman G, Shiloh Y, Groner Y, Segal M: Selective loss of dopaminergic nigro-

striatal neurons in brains of Atm-deficient mice. Proc Natl Acad Sci USA 95:12653-12656, 1998.

96. Eilam R, Peter Y, Groner Y, Segal M: Late degeneration of nigro-striatal neurons in ATM -/- mice.

Neuroscience 121:83-98, 2003.

97. Ekstrand MI, Terzioglu M, Galter D, Zhu S, Hofstetter C, Lindqvist E, Thams S, Bergstrand A, Hansson FS,

Trifunovic A, Hoffer B, Culheim S, Mohammed AH, Olson L, Larsson NG: Progressive parkinsonism in mice

with respiratory-chain-deficient dopamine neurons. Proc Natl Acad Sci USA 104:1325-1330, 2007.

Appendices

140

98. Ericson J, Rashbass P, Schedl A, Brenner-Morton S, Kawakami A, van Heyningen V, Jessel TM, Briscoe J:

Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signalling. Cell 90:169-

180, 1997.

99. Ethier I, Beaudry G, St Hilaire M, Milbrandt J, Rouillard C, Levesque D: The transcription factor NGFI-B

(Nur77) and retinoids play a critical role in acute neuroleptic-induced extrapyramidal effect and striatal

neuropeptide gene expression. Neuropsychopharmacology 29:335-346, 2004.

100. Fallon JH: Topographic organization of ascending dopaminergic projections. Ann N Y Acad Sci 537:1-9,

1988.

101. Fearnley JM, Lees AJ: Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain 114:2283-

2301, 1991.

102. Fentress JC, Stanfield BB, Cowan WM: Observations on the development of the striatum in mice and rats.

Anat Embryol 163:275-298, 1981.

103. Fernagut PO, Chalon S, Diguet E, Guilloteau D, Tison F, Jaber M: Motor behaviour deficits and their

histopathological and functional correlates in the nigrostriatal system of dopamine transporter knockout

mice. Neuroscience 116:1123-1130, 2003.

104. Fernández V, Bravo H, Kuljis R, Fuentes I: Autoradiographic study of the development of the neostriatum

in the rabbit. Brain Behav Evol 16:113-128, 1979.

105. Fernandez A, de Ceballos ML, Jenner P, Marsden CD: Neurotensin, substance P, delta and mu opioid

receptors are decreased in basal ganglia of Parkinson’s disease patients. Neuroscience 61:73-79, 1994.

106. Fernandez A, de Ceballos ML, Rose S, Jenner P, Marsden CD: Alterations in peptide levels in Parkinson’s

disease and inicidental Lewy body disease. Brain 119:823-830, 1996.

107. Ferri ALM, Lin W, Mavromatakis YE, Wang JC, Sasaki H, Whitsett JA, Ang SL: Foxa1 and Foxa2 regulate

multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner.

Development 134:2761-2769, 2007.

108. Finn JP 3rd, Edwards RH: Individual residues contribute to multiple differences in ligand recognition

between vesicular monoamine transporters 1 and 2. J Biol Chem 272:16301-16307, 1997.

109. Fishell G and Van der Kooy D: Pattern formation in the striatum: neurons with early projections to the

substantia nigra survive the cell death period. J Comp Neurol 312:33-42, 1991.

110. Fleming SM, Chesselet MF: Phenotypical characterization of genetic mouse models of Parkinson’s disease.

In: LeDoux M (ed) Animal models of movement disorders, 183-192, Academic, San Diego, 2005.

111. Fleming SM, Fernagut PO, Chesselet MF: Genetic mouse models of parkinsonism: strengths and limitations.

NeuroRx 2:495-503, 2005.

112. Fleming SM, Salcedo J, Fernagut PO, Rockenstein E, Masliah E, Levine MS, Chesselet MF: Early and

progressive sensorimotor anomalies in mice overexpressing wild-type human α-synuclein. J Neurosci

24:9434-9440, 2004.

113. Foster GA, Schultzberg M, Kökfelt T, Goldstein M, Hemmings HC Jr, Ouimet CC, Walaas SI, Greengard P:

Ontogeny of the dopamine and cyclic adenosine-3’:5’-monophosphate-regulated phosphoprotein (DARPP-

32) in the pre- and postnatal mouse central nervous system. Int J Dev Neursci 6:367-386, 1988.

114. Franklin KBJ, Paxinos G: The mouse brain in stereotaxic coordinates, Academic Press, London, 1997.

115. Fuchs J, Mueller JC, Lichtner P, Schulte C, Munz M, Berg D, Wullner U, Illig T, Sharma M, Gasser T: The

transcription factor PITX3 is associated with sporadic Parkinson's disease. Neurobiol Aging, 30:731-738,

2009.

116. Gage PJ, Camper SA: Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox

genes, is a potential regulator if anterior structure formation. Hum Mol Genet 6:457-464, 1997.

117. Galter D, Pernold K, Yoshitake T, Lindqvist E, Hoffer B, Kehr J, Larsson NG, Olson L: MitoPark mice mirror

the slow progression of key symptoms and L-DOPA response in Parkinson’s disease. Genes Brain Behav

9:173-181, 2010.

References

141

118. Gardner EL, Zukin RS, Makman MH: Modulation of opiate receptor binding in striatum and amygdala by

selective mesencephalic lesions. Brain Res 194:232-239, 1980.

119. Gaspar P, Jelloun NB, Febvret A: Sparing of the dopaminergic neurons containing Calbindin-D28K and of the

dopaminergic mesocortical projections in Weaver mutant mice. Neuroscience 61:293-305, 1994.

120. Gatto NM, Cockburn M, Bronstein J, Manthripragada AD, Ritz B: Well-water consumption and Parkinson’s

disease in rural California. Environ Health Perspect 117:1912-1918, 2009.

121. Gaweda-Walerych K, Safranow K, Maruszak A, Bialecka M, Klodowska-Duda G, Czyzewski K, Slawek J,

Rudzinska M, Styczynska M, Opala G, Drozdzik M, Kurzawski M, Szczudlik A, Canter JA, Barcikowska M,

Zekanowski C: Mitochondrial transcription factor A variants and the risk of Parkinson’s disease. Neurosci

Lett 469:24-29, 2009.

122. Gebauer F, Hentze MW: Molecular mechanisms of translational control. Nat Rev Mol Cell Biol 5:827-835,

2004.

123. Geng DY, Li YX, Zee CS: Magnetic resonance imaging-based volumetric analysis of basal ganglia nuclei and

substantia nigra in patients with Parkinson’s disease. Neurosurgery 58:256-262, 2006.

124. Gerfen CR: The neostriatal mosaic: compartmentalization of corticostriatal input and striatonigral output

systems. Nature 311:461-464, 1984.

125. Gerfen CR: The neostriatal mosaic: I. Compartmental organization of projections from the striatum to the

substantia nigra in the rat. J Comp Neurol 236:454-476, 1985.

126. Gerfen CR: The neotriatal mosaic: multiple levels of compartmental organization. Trends Neurosci 15:133-

139, 1992.

127. Gerfen CR: Dopamine-mediated gene regulation in models of Parkinson’s disease. Ann Neurol 47:S42-S50,

2000.

128. Gerfen CR: Molecular effects of dopamine on striatal projection pathways. Trends Neurosci 23:S64-S70,

2000.

129. Gerfen CR, Baimbridge KG, Miller JJ: The neostriatal mosaic: Compartmental distribution of calcium-

binding protein and parvalbumin in the basal ganglia of the rat and monkey. Proc Natl Acad Sci USA

82:8780-8784, 1985.

130. Gerfen CR, Baimbridge KG, Thibault J: The neostriatal mosaic: III. Biochemical and developmental

dissociation of patch matrix mesostriatal systems. J Neurosci 7:3935-3944, 1987.

131. Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma F J Jr, Sibley DR: D1 and D2 dopamine-

receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250:1429-1432,

1990.

132. Gerfen CR, Herkenham M, Thibault J: The neostriatal mosaic: II. Patch and matrix-directed mesiostriatal

dopaminergic and non-dopaminergic systems. J Neurosci 7:3915-3934, 1987.

133. German DC, Manaye KF, Sonsalla PK, Brooks BA: Midbrain dopaminergic cell loss in Parkinson’s disease

and MPTP-induced parkinsonism: sparing of calbindin-D(28K)-containing cells. Ann N Y Acad Sci 648:42-62,

1992.

134. Ghetti B, Triarhou LC: Degeneration of mesencephalic dopamine neurons in weaver mutant mice.

Neurochem Int 20:305S-307S, 1992.

135. Giros B, Jaber M, Jones SR, Wightman RM, Caron MG: Hyperlocomotion and indifference to cocaine and

amphetamine in mice lacking the dopamine transporter. Nature 379:606-612, 1996.

136. Gispert S, Ricciardi F, Kurz A, Azizov M, Hoepken HH, Becker D, Voos W, Leuner K, Müller WE, Kudin AP,

Kunz WS, Zimmermann A, Roeper J, Wenzel D, Jendracht M, Garcia-Arencíbia M, Fernández-Ruiz J, Huber L,

Rohrer H, Barrera M, Reichert AS, Rüb U, Chen A, Nussbaum RL, Auburger G: Parkinson phenotype in aged

PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of

neurodegeneration. PloS One 4:e5777, 2009.

Appendices

142

137. Glatt CE, Wahner AD, White DJ, Ruiz-Linares A, Ritz B: Gain-of-function haplotypes in the vesicular

monoamine transporter promotor are protective for Parkinson’s disease in women. Hum Mol Genet

15:299-305, 2006.

138. Goedart M, Mantyh PW, Emson PC, Hunt SP: Inverse relationship between neurotensin receptors and

neurotensin-like immunoreactivity in cat striatum. Nature 307:543-546, 1984.

139. Goldberg MS, Fleming SM, Palacino JJ, Cepeda C, Lam HA, Bhatnagar A, Meloni EG, Wu N, Ackerson LC,

Klapstein GJ, Gajendiran M, Roth BL, Chesselet MF, Maidment NT, Levine MS, Shen J: Parkin-deficient mice

exhibit nigrostriatal deficits but no loss of dopaminergic neurons. J Biol Chem 278:43628-43635, 2003.

140. Goldberg MS, Pisani A, Haburcak M, Vortherms TA, Kitada T, Costa C, Tong Y, Martella G, Tscherter A,

Martins A, Bernardi G, Roth BL, Pothos EN, Calabresi P, Shen J: Nigrostriatal dopaminergic deficits and

hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron 45:489-496,

2005.

141. Graybiel AM: Neurotransmitters and neuromodulators in the basal ganglia. Trends Neurosci 84:244-254,

1990.

142. Graybiel AM, Otha K, Roffler-Tarlov S: Patterns of cell and fiber vulnerability in the mesostriatal system of

the mutant mouse weaver. I. Gradients and compartments. J Neurosci 10:720-733, 1990.

143. Graybiel AM, Pickel VM, Joh TH, Reis DJ, Ragsdale Jr CW: Direct demonstration of correspondence

between the dopamine islands and acetylcholinesterase patches in the developing striatum. Proc Natl

Acad Sci 78:5871-5875, 1981.

144. Graw J: Mouse models of congenital cataract. Eye 13:438-444, 1999.

145. Grimm C, Chatterjee B, Favor J, Immervoll T, Löster J, Klopp N, Sandulache R, Graw J: Aphakia (ak), a

mouse mutation affecting early eye development: fine mapping consideration of candidate genes and

altered Pax6 and Six3 gene expression pattern. Dev Genet 23:299-316, 1998.

146. Gritli-Linde A, Lewis P, McMahon AP, Linde A: The whereabouts of a morphogen: direct evidence for

short- and graded long-range activity of hedgehog signalling peptides. Dev Biol 236:364-386, 2001.

147. Guillin O, Diaz J, Carroll P, Griffon N, Schwartz JC, Sokoloff P: BDNF controls dopamine D3 receptor

expression and triggers behavioural sensitization. Nature 411:86-89, 2001.

148. Gundersen HJ, Bagger P, Bendtsen TF, Evans SM, Korbo L, Marcussen N, Möller A, Nielsen K, Nyengard JR,

Pakkenberg B: The new stereological tools: disector, fractionator, nucleator and point sampled intercepts

and their use in pathological research and diagnosis. APMIS 96:857-881, 1988.

149. Guttman M, Seeman P: L-dopa reverses the elevated density of D2 dopamine receptors in Parkinson’s

diseased striatum. J Neural Transm 64:93-103, 1985.

150. Guyenet PG, Crane JK: Non-dopaminergic nigrostriatal pathway. Brain Res 213:291-305, 1981.

151. Haber SN, Watson J: The comparative distribution of enkephalin, dynorphin and substance P in the human

globus pallidus and basal forebrain. Neuroscience 14:1011-1024, 1985.

152. Hanson GR, Keefe KA: Dopamine D-1 regulation of caudate neurotensin mRNA in the presence or absence

of the nigrostriatal dopamine pathway. Brain Res Mol Brain Res 66:111-121, 1999.

153. Haobam R, Sindhu KM, Chandra G, Mohanakumar KP: Swim-test as a function of motor impairment in

MPTP model of Parkinson’s disease: a comparative study in two mouse strains. Behav Brain Res 163:159-

167, 2005.

154. Hassler R: Zur Pathologie der Paralysis agitans und des postenzephalitischen Parkinsonismus. J Psychol

Neurol 48:387-476, 1938.

155. Haubenberger D, Reinthaler E, Mueller JC, Pirker W, Katzenschlager R, Froehlich R, Bruecke T, Daniel G,

Auff E, Zimprich A: Associations of transcription factor polymorphisms PITX3 and EN1 with Parkinson’s

disease. Neurobiol Aging 32:302-307, 2011.

156. Heikkila RE, Hess A, Duvoisin RC: Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-

tetrahydropyridine in mice. Science 224:1451-1453, 1984.

References

143

157. Herkenham M and Pert CB: Mosaic distribution of opiate receptors, parafascicular projections and

acetylcholinesterase in rat striatum. Nature 291:415-418, 1981.

158. Hidalgo-Sánchez M, Simeone A, Alvarado-Mallart RM: Fgf8 and Gbx2 induction concomitant with Otx2

repression is correlated with midbrain-hindbrain fate of caudal prosencephalon. Development 126:3191-

3203, 1999.

159. http://tools.invitrogen.com/content/sfs/manuals/38-2850%20-%201206.pdf

160. Hurley MJ, Stubbs CM, Jenner P, Marsden CD: D3 receptor expression within the basal ganglia is not

affected by Parkinson’s disease. Neurosci Lett 214:75-78, 1996.

161. Hwang DY, Ardayfio P, Kang UJ, Semina EV, Kim KS: Selective loss of dopaminergic neurons in the

substantia nigra of Pitx3-deficient aphakia mice. Mol Brain Res 114:123-131, 2003.

162. Hwang DY, Fleming SM, Ardayfio P, Moran-Gates T, Kim H, Tarazi FI, Chesselet MF, Kim KS: 3,4-

dihydroxyphenylalanine reverses the motor deficits in Pitx3-deficient aphakia mice: behavioral

characterization of a novel genetic model of Parkinson’s disease. J Neurosci 25:2132-2137, 2005.

163. Hwang DY, Hong S, Jeong JW, Choi S, Kim H, Kim J, Kim KS: Vesicular monoamine transporter 2 and

dopamine trasporter are molecular targets of Pitx3 in the ventral midbrain dopamine neurons. J

Neurochem 111:1202-1212, 2009.

164. Hynes M, Rosenthal A: Specification of dopaminergic and serotonergic neurons in the vertebrate CNS. Curr

Neurol 9:26-36, 1999.

165. Iancu R, Mohapel P, Brundin P, Paul G: Behavioral characterization of a unilateral 6-OHDA-lesion model of

Parkinson’s disease in mice. Behav Brain Res 162:1-10, 2005.

166. Inden M, Kitamura Y, Takeuchi H, Yanagida T, Takata K, Kobayashi Y, Taniguchi T, Yoshimoto K, Kaneko M,

Okuma Y, Taira T, Ariga H, Shimohama S: Neurodegeneration of mouse nigrostriatal dopaminergic system

induced by repeated oral administration of rotenone is prevented by 4-phenylbutyrate, a chemical

chaperone. J Neurochem 101:1491-1504, 2007.

167. Ingham CA, Hood SH, Arbuthnott GW: Spine density on neostriatal neurons changes with 6-

hydroxydopamine lesions and with age. Brain Res 503:334-338, 1989.

168. Iwawaki T, Kohno K, Kobayashi K: Identification of a potential nurr1 response element that activates the

tyrosine hydroxylase gene promoter in cultured cells. Biochem biophys Res Commun 274:590-595, 2000.

169. Jaber M, Dumartin B, Sagné C, Haycock JW, Roubert C, Giros B, Bloch B, Caron MG: Differential regulation

of tyrosine hydroxylase in the basal ganglia of mice lacking the dopamine transporter. Eur J Neurosci

11:3499-3511, 1999.

170. Jackson-Lewis V, Vila M, Djaldetti R, Guegan C, Liberatore G, Liu J, O’Malley KL, Burke RE, Przedborski S:

Developmental cell death in dopaminergic neurons of the substantia nigra. J Comp Neurol 424:476-488,

2000.

171. Jacobs FMJ, Smits SM, Noorlander CW, Von Oerthel L, Van der Linden AJA, Burbach JPH, Smidt MP:

Retinoic acid counteracts developmental defects in the substantia nigra caused by Pitx3 deficiency.

Development 134:2673-2684, 2007.

172. Jacobs FMJ, Van Erp S, Van der Linden AJA, Von Oerthel L, Burbach JPH, Smidt MP: Pitx3 potentiates Nurr1

in dopamine neuron terminal differentiation through release of SMRT-mediated repression. Development

136:531-540, 2009.

173. Janec E, Burke RE: Naturally occurring cell death during postnatal development of the substantia nigra

pars compacta of rat. Mol Cell Neurosci 4:30-35, 1993.

174. Jankovic J, Chen S, Le WD: The role of Nurr1 in the development of dopaminerguc neurons and

Parkinson’s disease. Prog Neurobiol 77:128-138, 2005.

175. Jellinger KA: The pathology of Parkinson's disease. In: Calne D, Calne S (eds) Parkinson’s Disease, Advances

in Neurology Vol 86, 55-72, Lippincott, Williams and Wilkins, Philadeplhia PA, 2001.

176. Jenner P: Parkinson’s disease, pesticides and mitochondrial dysfunction. Trends Neurosci 24:245-247,

2001.

Appendices

144

177. Jessel TM: Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat Rev

Genet 1:20-29, 2000.

178. Jiang C, Wan X, He Y, Pan T, Jankovic J, Le W: Age-dependent dopaminergic dysfunction in Nurr1 knockout

mice. Exp Neurol 191:154-162, 2005.

179. Joel D, Weiner I: The connections of the dopaminergic system with the striatum in rats and primates: an

analysis with respect to the functional and compartmental organization of the striatum. Neuroscience

96:451-474, 2000.

180. Jones SR, Gainetdinov RR, Jaber M, Giros B, Wightman RM, Caron MG: Profound neuronal plasticity in

response to inactivation of the dopamine transporter. Proc Natl Acad Sci USA 95:4029-4034, 1998.

181. Joyner AL, Herrup K, Auerbach BA, Davis CA, Rossant J: Subtle cerebellar phenotype in mice homozygous

for a targeted deletion of the En-2 homeobox. Science 251:1239-1243, 1991.

182. Joyner AL: Engrailed, Wnt and Pax genes regulate midbrain-hindbrain development. Trends Genet 12:15-

20, 1996.

183. Kala K, Haugas M, Lilleväli K, Guimera J, Wurst W, Salminen M, Partanen J: Gata2 is a tissue-specific post-

mitotic selector gene for midbrain GABAergic neurons. Development 136:253-262, 2009.

184. Kappen C, Ruddle FH: Evolution of a regulatory gene family: HOM/HOX genes. Curr Opin Genet Dev 3:931-

938, 1993.

185. Kariya S, Hirano M, Takahashi N, Furiya Y, Ueno S: Lack of association between polymorphic microsatellites

of the VMAT2 gene and Parkinson’s disease in Japan. J Neurol Sci 232:91-94, 2005.

186. Karlsson RM, Hefner K, Sibley DR, Holmes A: Comparison of dopamine D1 and D5 receptor knockout mice

for cocaine locomotor sensitization. Psychopharmacology, 200:117-127, 2008.

187. Kas MJ, van der Linden AJ, Oppelaar H, von Oerthel L, Ramakers GM, Smidt MP: Phenotypic segregation of

aphakia and Pitx3-null mutants reveal that Pitx3 deficiency increases consolidation of specific movement

components. Behav Brain Res 186:208-214, 2008.

188. Kaseda Y, Ghetti B, Low WC, Richter JA, Simon JR: Dopamine D2 receptors increase in the dorsolateral

striatum of weaver mutant mice. Brain Res 422:178-181, 1987.

189. Katahira T, Sato T, Sugiyama S, Okafuji T, Araki I, Funahashi J, Nakamura H: Interaction between Otx2 and

Gbx2 defines the organizing center for the optic tectum. Mech Dev 91:43-52, 2000.

190. Kawano H, Ohyama K, Kawamura K, Nagatsu I: Migration of dopaminergic neurons in the embryonic

mesencephalon of mice. Brain Res Dev Brain Res 86:101-113, 1995.

191. Kele J, Simplicio N, Ferri ALM, Mira H, Guillemot F, Arenas E, Ang SL: Neurogenin 2 is required for the

development of ventral midbrain dopaminergic neurons. Development 133:495-505, 2006.

192. Kelly MA, Rubinstein M, Phillips TJ, Lessov CN, Burkhart-Kasch S, Zhang G, Bunzow JR, Fang Y, Gerhardt GA,

Grandy DK, Low MJ: Locomotor activity in D2 dopamine receptor-deficient mice is determined by gene

dosage, genetic background, and developmental adaptations. J Neurosci 18:3470-3479, 1998.

193. Kemp JM, Powel TPS: The site of termination of afferent fibres in the caudate nucleus. Phil Trans R Soc

Lond B Biol Sci 262:413-427, 1971.

194. Kent JL, Pert CB, Herkenham M: Ontogeny of opiate receptors in rat forebrain: visualization by in vitro

autoradiography. Dev Brain Res 2:487-504, 1982.

195. Kim J, Inoue K, Ishii J, Vanti WB, Voronov SV, Murchison E, Hannon G, Abeliovich A: A microRNA feedback

circuit in midbrain dopamine neurons. Science 317:1220-1224, 2007.

196. King DP, Zhao Y, Sangoram AM, Wilsbacher LD, Tanaka M, Antoch MP, Steeves TD, Vitaterna MH,

Kornhauser JM, Lowrey PL, Turek FW, Takahashi JS: Positional cloning of the mouse circadian clock gene.

Cell 89:641-653, 1997.

197. Kish SJ, Shannak K, Hornykiewicz O: Uneven pattern of dopamine loss in the striatum of patients with

idiopathic Parkinson's disease. Pathophysiologic and clinical implications. N Engl J Med 318:876-880, 1988.

198. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N:

Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:605-608, 1998.

References

145

199. Kitada T, Pisani A, Porter DR, Yamaguchi H, Tscherter A, Martella G, Bonsi P, Zhang C, Pothos EN, Shen J:

Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice. Proc Natl Acad

Sci USA 104:11441-11446, 2007.

200. Kitamura K, Miura H, Yanazawa M, Miyashita T, Kato K: Expression patterns of Brx1 (Rieg gene), Sonic

hedgehog, Nkx2.2, Dlx1 and Arx during zona limitans intrathalamica and embryonic geniculate nuclear

formation. Mech Dev 67:83-96, 1997.

201. Koller WC: How accurately can Parkinson’s disease be diagnosed. Neurology 42:6-16, 1992.

202. Konstantoulas CJ, Parmar M, Li M: FoxP1 promotes midbrain identity in embryonic stem cell-derived

dopamine neurons by regulating Pitx3. J Neurochem 113:836-847, 2010.

203. Korotkova TM, Ponomarenko AA, Haas HL, Sergeeva OA: Differential expression of the homeobox gene

Pitx3 in midbrain dopaminergic neurons. Eur J Neurosci 22:1287-1293, 2005.

204. Kozak M: Interpreting cDNA sequences: some insights from studies on translation. Mamm Genome 7:563-

574, 1996.

205. Krüger R, Kuhn W, Muller T, Woitalla D, Graeber M, Kosel S, Przuntek H, Epplen JT, Schols L, Riess O:

Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson’s disease. Nat Genet 18:106-108,

1998.

206. Lalonde R: Motor abnormalities in weaver mutant mice. Exp Brain Res 65:479-481, 1987.

207. Lamonerie T, Tremblay JJ, Lanctôt C, Therrien M, Gauthier Y, Drouin J: Ptx1, a bicoid-related homeo box

transcription factor involved in transcription of the pro-opiomelanocortin gene. Genes Dev 10:1284-1295,

1996.

208. Lança AJ, Boyd S, Kolb BE, Van der Kooy D: The development of a patchy organization of the rat striatum.

Brain Res Dev Brain Res 27:1-10, 1986.

209. Lanctôt C, Lamolet B, Drouin J: The bicoid-related homeoprotein Ptx1 defines the most anterior domain of

the embryo and differentiates posterior from anterior lateral mesoderm. Development 124:2807-2817,

1997.

210. Lanctôt C, Moreau A, Chamberland M, Tremblay ML, Drouin J: Hindlimb patterning and mandible

development require the Ptx1 gene. Development 126:1805-1810, 1999.

211. Landau AM, Luk KC, Jones ML, Siegrist-Johnstone R, Young YK, Kouassi E, Rymar VV, Dagher A, Sadikot AF,

Desbarats J: Defective Fas expression exacerbates neurotoxicity in a model of Parkinson's disease. J Exp

Med 202:575-581, 2005.

212. Lang AE, Lozano AM: Parkinson’s disease. First of two parts. N Engl J Med 339:1044-1053, 1998.

213. Lauder JM: Neurotransmitters as morphogens. Prog Brain Res 73:365-387, 1988.

214. Laverty R: On the roles of dopamine and noradrenaline in animal behaviour. Prog Neurobiol 3:33-70, 1975.

215. Lavoie B, Parent A: Dopaminergic neurons expressing calbindin in normal and parkinsonian monkeys.

Neuroreport 2:601-604, 1991.

216. Law SW, Conneely OM, DeMayo FJ, O’Mally BW: Identification of a new brain-specific transcription factor,

NURR1. Mol endocrinol 6:2129-2135, 1992.

217. Le W, Conneely OM, He Y, Jankovic J, Appel SH: Reduced Nurr1 expression increased the vulnerability of

mesencephalic dopamine neurons to MPTP-induced injury. J Neurochem 73:2218-2221, 1999.

218. Le W, Nguyen D, Lin XW, Rawal P, Huang M, Ding Y, Xie W, Deng H, Jankovic J: Transcription factor PITX3

gene in Parkinson’s disease. Neurobiol Aging Epub ahead of print, 2009.

219. Le W, Pan T, Huang M, Xu P, Xie W, Zhu W, Zhang X, Deng H, Jankovic J: Decreased NURR1 gene

expression in patients with Parkinson’s disease. J Neurol Sci 273:29-33, 2008.

220. Lebel M, Gauthier Y, Moreau A, Drouin J: Pitx3 activates mouse tyrosine hydroxylase promoter via a high –

affinity binding site. J Neurochem 77:558-567, 2001.

221. Lee CS, Samii A, Sossi V, Ruth TJ, Schulzer M, Holden JE, Wudel J, Pal PK, de la Funete-Fernandez R, Calne

DB, Stoessl AJ: In vivo positron emission tomographic evidence for compensatory changes in presynaptic

dopaminergic nerve terminals in Parkinson’s disease. Ann Neurol 47:493-503, 2000.

Appendices

146

222. Levesque D, Martres MP, Diaz J, Griffon N, Lammers CH, Sokoloff P, Schwartz JC: A paradoxical regulation

of the dopamine D3 receptor expression suggests the involvement of an anterograde factor from

dopamine neurons. Proc Natl Acad Sci USA 92:1719-1723, 1995.

223. Li Y, Liu W, Oo TF, Wang L, Tang Y, Jackson-Lewis V, Zhou C, Geghman K, Bogdanov M, Przedborski S, Beal

MF, Burke RE, Li C: Mutant LRRK2R1441G BAC transgenic mice recapitulate cardinal features of

Parkinson’s disease. Nat Neurosci 12:826-828, 2009.

224. Liang CL, Sinton CM, German DC: Midbrain dopaminergic neurons in the mouse: Co-localization with

calbindin-D-28K and calretinin. Neuroscience 75:523-533, 1996.

225. Liang CL, Sinton CM, Sonsalla PK, German DC: Midbrain dopaminergic neurons in the mouse that contain

calbindin-D-28k exhibit reduced vulnerability to MPTP-induced neurodegeneration. Neurodegeneration

5:313-318, 1996.

226. Linden R: The survival of developing neurons: a review of afferent control. Neuroscience 58:671-682, 1994.

227. Lisanby SH, McDonald WM, Massey EW, Doraiswamy PM, Rozear M, Boyko OB, Krishnan KR, Nemeroff C:

Diminished subcortical nuclei volumes in Parkinson’s disease by MR imaging. J Neural Trans Suppl 40:13-

21, 1993.

228. Liss B, Neu A, Roeper J: The weaver mouse gain-of-function phenotype of dopaminergic midbrain neurons

is determined by coactivation of wvGirk2 and KATP channels. J Neurosci 19:8839-8848, 1999.

229. Lu X-H, Fleming SM, Meurers B, Ackerson LC, Mortazavi F, Lo V, Hernandez D, Sulzer D, Jackson GR,

Maidment NT, Chesselet M-F, Yang XW: BAC transgenic mice expressing a truncated mutant Parkin exhibit

age-dependent hypokinetic motor deficits, dopaminergic neuron degeneration, and accumulation of

proteinase K-resistant alpha-synuclein. J Neurosci 29:1962-1976, 2009.

230. Luk KC and Sadikot AF: GABA promotes survival but not proliferation of parvalbumin-immunoreactive

interneurons in rodent neostriatum: an in vivo study with stereology. Neuroscience 104:93-103, 2001.

231. Lundblad M, Picconi B, Lindgren H, Cenci MA: A model of L-DOPA-induced dyskinesias in 6-

hydroxydopamine lesioned mice: relation to motor and cellular parameters of nigrostriatal function.

Neurobiol Dis 16:110-123, 2004.

232. Ma L, Zhou J: Dopamine promotes the survival of embryonic striatal cells: involvement of superoxide and

endogenous NADPH oxidase. Neurochem Res 31:463-471, 2006.

233. Mages HW, Rilke O, Bravo R, Senger G, Kroczek RA: NOT, a human immediate-early response gene closely

related to the steroid/thyroid hormone receptor NAK1/TR3. Mol Endocrinol 8:1583-1591, 1994.

234. Martí E, Takada R, Bumcrot DA, Sasaki H, McMahon AP: Distribution of Sonic hedgehog peptides in the

developing chick and mouse embryo. Development 121:2537-2547, 1995.

235. Martí J, Wills KV, Ghetti B, Bayer SA: The weaver gene has no effect on the generation patterns of

mesencephalic dopaminergic neurons. Brain Res Dev Brain Res 122:165-172, 2000.

236. Martinez S, Crossley PH, Cobos I, Rubenstein JL, Martin GR: FGF8 induces formation of an ectopic isthmic

organizer and isthmocerebellar development via a repressive effect on Otx2 expression. Development

126:1189-1200, 1999.

237. Martres MP, Bouthenet ML, SalesN, Sokoloff P, Schwartz JC: Widespread distribution of brain dopamine

receptors evidenced with [125

]iodosulpride, a highly selective ligand. Science 228:752-755, 1985.

238. Masliah E, Rockenstein E, Veinbergs I, Mallory M, Hashimoto M, Takeda A, Sagara Y, Sisk A, Mucke L:

Dopaminergic loss and inclusion body formation in α-synuclein mice: implications for neurodegenerative

disorders. Science 287:1265-1269, 2000.

239. Matsuo I, Kuratani S, Kimura C, Takeda N, Aizawa S: Mouse Otx2 functions in the formation and patterning

of rostral head. Genes Dev 9:2646-2658, 1995.

240. Maxwell SL, Ho HY, Kuehner E, Zhao SL, Li M: Pitx3 regulates tyrosine hydroxylase expression in the

substantia nigra and identifies a subgroup of mesencephalic dopaminergic progenitor neurons during

mouse development. Dev Biol 282:467-479, 2005.

References

147

241. McCafferty PJ, Adams J, Maden M, Rosa-Molinar E: Too much of a good thing: retinoic acid as an

endogenous regulator of neural differentiation and exogenous teratogen. Eur J Neurosci 18:457-472, 2003.

242. McDougle CJ, Barr LC, Goodman WK, Price LH: Possible role of neuropeptides in obsessive compulsive

disorder. Psychoneuroendocrinology 24:1-24, 1999.

243. McMahon AP, Joyner AL, Bradley A, McMahon JA: The midbrain-hindbrain phenotype of Wnt-1-/Wnt-1-

mice results from stepwise deletion of engrailed-expressing cells by 9.5 days postcoitum. Cell 69:581-595,

1992.

244. Meredith GE, Totterdell S, Potashkin JA, Surmeier DJ: Modeling PD pathogenesis in mice: advantages of a

chronic MPTP model. Parkinsonism Relat Dis 14:S112-S115, 2008.

245. Meyers EN, Lewandoski M, Martin GR: An Fgf8 mutant allele series generated by Cre- and Flp-mediated

recombination. Nat Genet 18:136-141, 1998.

246. Michael MI, Khalil SH, Matta CA, Rizk TA: Normal postnatal development of the mouse eye. Folia Morphol

(Praha) 36:125-132, 1988.

247. Millen KJ, Wurst W, Herrup K, Joyner AL: Abnormal embryonic cerebellar development and patterning of

postnatal foliation in two mouse Engrailed-2 mutants. Development 120:695-706, 1994.

248. Millet S, Bloch-Gallego E, Simeone A, Alvarado-Mallart RM: The caudal limit of Otx2 gene expression as a

marker of the midbrain-hindbrain boundary: a study using in situ hybridisation and chick/quail homotopic

grafts. Development 122:3785-3797, 1996.

249. Montgomery EB Jr, Baker KB, Lyons K, Koller WC: Abnormal performance on the PD test battery by

asymptomatic first- degree relatives. Neurology 52:757-762, 1999.

250. Morin X, Cremer H, Hirsch MR, Kapur RP, Goridis C, Brunet JF: Defects in sensory and autonomic ganglia

and absence of locus coeruleus in mice deficient for the homeobox gene Phox2a. Neuron 18:411-423,

1997.

251. Morissette M, Goulet M, Grondin R, Blanchet P, Bedard PJ, Di Paolo T, Levesque D: Associative and limbic

regions of monkey striatum express high levels of D3 receptors: effects of MPTP and dopamine agonists

replacement therapies. Eur J Neurosci 10:2565-2573, 1998.

252. Muccielli ML, Martinez S, Pattyn A, Goridis C, Brunet JF: Otlx2, an Otx-related homeobox gene expressed

in the pituitary gland and in a restricted pattern in the forebrain. Mol Cell Neurosci 8:258-271, 1996.

253. Nagatsu T, Levitt M, Udenfriend S: Tyrosine hydroxylase. The initial step in norepinephrine biosynthesis. J

Biol Chem 239:2910-2917, 1964.

254. Nagy A: Cre recombinase: The universal reagent for genome tailoring. Genesis 26:99-109, 2000.

255. Nelander J, Hebsgaard JB, Parmar M: Organization of the human embryonic ventral mesencephalon. Gene

Expr Patterns 9:555-561, 2009.

256. Nelson EL, Liang CL, Sinton CM, German DC: Midbrain dopaminergic neurons in the mouse: Computer-

assisted mapping. J Comp Neurol 369:361-371, 1996.

257. Nuber S, Petrasch-Parwez E, Winner B, Winkler J, von Hörsten S, Schmidt T, Boy J, Kuhn M, Nguyen HP,

Teismann P, Schulz JB, Neumann M, Pichier BJ, Reischl G, Holzmann C, Schmitt I, Bornemann A, Kuhn W,

Zimmerman F, Servadio A, Riess O: Neurodegeneration and motor dysfunction in a conditional model of

Parkinson’s disease. J Neurosci 28:2471-2484, 2008.

258. Nunes I, Tovmasian LT, Silva RM, Burke RE, Goff SP: Pitx3 is required for development of substantia nigra

dopaminergic neurons. Proc Natl Acad Scie USA 100:4245-4250, 2003.

259. Nygaard TG: Dopa-responsive dystonia. Curr Opin Neurol 8:310-313, 1995.

260. Ogawa N, Hirose Y, Ohara S, Oni T, Watanabe Y: A simple quatitative bradykinesia test in MPTP-treated

mice. Res Commun Chem Pathol Pharmacol 50:435-441, 1985.

261. Ohtani N, Goto T, Waeber C, Bhide PG: Dopamine modulates cell cycle in the lateral ganglionic eminence. J

Neurosci 23:2840-2850, 2003.

262. Olanow CW, Stern MB, Sethi K: The scientific and clinical basis for the treatment of Parkinson’s disease

(2009). Neurology 72:S1-S136, 2009.

Appendices

148

263. Olson L, Seiger A, Fuxe F: Heterogeneity of striatal and limbic dopamine innervation: highly fluorescent

island in developing and adult rats. Brain Res 44:283-288, 1972.

264. Oo TF, Burke RE: The time course of developmental cell death in phenotypically defined dopaminergic

neurons of the substantia nigra. Brain Res Dev Brain Res 98:191-196, 1997.

265. Oorschot DE: Total number of neurons in the neostriatal, pallidal, subthalamic, and substantia nigra nuclei

of the rat basal ganglia: a stereological study using the cavalieri and optical dissector methods. J Comp

Neurol 366:580-599, 1996.

266. Oppenheim RW: Cell death during development of the nervous system. Annu Rev Neurosci 14:453-501,

1991.

267. Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, de Munain AL, Aparicio S, Gill AM,

Khan N, Johnson J, Martinez JR, Nicholi D, Carrera IM, Pena AS, de Silva R, Lees A, Marti-Masso JF, Perez-

Tur J, Wood NW, Singleton AB: Cloning of the gene containing mutations that cause PARK8-linked

Parkinson’s disease. Neuron 44:595-600, 2004.

268. Pan-Montojo F, Anichtchik O, Dening Y, Knels L, Pursche S, Jung R, Jackson S, Gille G, Spillantini MG,

Reichmann H, Funk RH: Progression of Parkinson’s disease pathology is reproduced by intragastric

administration of rotenone in mice. PLos One 5:e8762, 2010.

269. Parent A, Hazrati LN: Funtional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical

loop. Brain Res Brain Res Rev 20:91-127, 1995.

270. Parkinson J: Essay on the shaking palsy. C.o.M. Library, London, 1817.

271. Peng C, Fan S, Li X, Fan X, Ming M, Sun Z, Le W: Overexpression of Pitx3 regulates expression of BDNF and

GDNF in SH-SY5Y cells and primary ventral mesencephalic cultures. FEBS Lett 581:1357-1361, 2007.

272. Pert CB, Kuhar MJ, Snyder SH: Opiate receptors: autoradiographic localization in rat brain. Proc Natl Acad

Sci USA 73:3729-3733, 1976.

273. Piccini P, Burn DJ, Ceravolo R, Maraganore D, Brooks DJ: The role of inheritance in sporadic Parkinson's

disease: evidence from a longitudinal study of dopaminergic function in twins. Ann Neurol 45:577-582,

1999.

274. Piedra ME, Icardo JM, Albajar M, Rodriguez-rey JC, Ros MA: Pitx2 participates in the late phase of the

pathway controlling left-right asymmetry. Cell 94:319-324, 1998.

275. Pierani A, Brenner-Morton S, Chiang C, Jessel TM: A sonic hedgehog-independent, retionoid-activated

pathway of neurogenesis in the ventral spinal cord. Cell 97:903-915, 1999.

276. Piggott MA, Marshall EF, Thomas N, Lloyd S, Court JA, Jaros E, Burn D, Johnson M, Perry RH, McKeith IG,

Ballard C, Perry EK: Striatal dopaminergic markers in dementia with Lewy bodies, Alzheimer’s and

Parkinson’s disease: rostrocaudal distribution. Brain 122:1449-1468, 1999.

277. Placzek M: The role of the notochord and floor plate in inductive interactions. Curr Opin Genet Dev 5:499-

506, 1995.

278. Pollard H, Llorens C, Schwartz JC, Gros C, Dray F: Localization of opiate receptors and enkephalins in the

rat striatum in relationship with the nigrostriatal dopaminergic system: lesion studies. Brain Res 151:392-

398, 1978.

279. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R,

Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM,

Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL: Mutation in the alpha-synuclein gene identified in families

with Parkinson's disease. Science 276:2045-2047, 1997.

280. Popolo M, McCarthy DM, Bhide PG: Influence of dopamine on precursor cell proliferation and

differentiation in the embryonic mouse telencephalon. Dev Neurosci 26:229-244, 2004.

281. Reifers F, Böhli H, Walsh EC, Crossley PH, Stainier DY, Brand M: Fgf8 is mutated in zebrafish acerebellar

(ace) mutants and is required for maintenance of midbrain-hindbrain boundary development and

somitogenesis. Development 125:2381-2395, 1998.

References

149

282. Ren JP, Zhao YW, Sun XJ: Toxic influence of chronic oral administration of paraquat on nigrostriatal

dopaminergic neurons in C57BL/6 mice. Chin Med J (Engl) 122:2366-2371, 2009.

283. Richfield EK, Thiruchelvam MJ, Cory-Slechta DA, Wuertzer C, Gainetdinov RR, Caron MG, Di Monte DA,

Federoff HJ: Behavioral and neurochemical effects of wildtype and mutated human alpha-synuclein in

transgenic mice. Exp Neurol 175:35-48, 2002.

284. Rieger DK, Reichenberger E, McLean W, Sidow A, Olsen BR: A double-deletion mutation in the Pitx3 gene

causes arrested lens development in aphakia mice. Genomics 72:61-72, 2001.

285. Rinne JO, Rinne JK, Laakso K, Lönnberg P, Rinne UK: Dopamine D-1 receptors in the parkinsonian brain.

Brain Res 359:306-310, 1985.

286. Rinne UK, Rinne JO, Rinne JK, Laakso K, Lönnberg P: Brain neurostransmitters and neuropeptides in

Parkinson’s disease. Acta Physiol Pharamcol Latinoam 34:287-299, 1984.

287. Roelink H: Tripartite signalling of pattern: interactions between Hedgehogs, BMPs and Wnts in the control

of vertebrate development. Curr Opin Neurobiol 6:33-40, 1996.

288. Roffler-Tarlov S, Graybiel AM: Expression of the weaver gene in dopamine-containing neural systems is

dose-dependent and affects both striatal and nonstriatal regions. J Neurosci 6:3319-3330, 1986.

289. Roffler-Tarlov S, Martin B, Graybiel AM, Kauer JS: Cell death in the midbrain of the murine mutation

weaver. J Neurosci 16:1819-1826, 1996.

290. Roffler-Tarlov S, Pugatch D, Graybiel AM: Patterns of cell and fiber vulnerability in the mesostriatal system

of the mutant mouse weaver. II. High affinity uptake sites for dopamine. J Neurosci 10:734-740, 1990.

291. Rousso DL, Gaber ZB, Wellik D, Morrisey EE, Novitch BG: Coordinated actions of the forkhead protein

FoxP1 and Hox proteins in the comunar organization of spinal motor neurons. Neuron 59:226-240, 2008.

292. Rubenstein JL, Martinez S, Shimamura K, Puelles L: The embryonic vertebrate forebrain: the prosomeric

model. Science 266:578-580, 1994.

293. Ryan AK, Blumberg B, Rodriquez-Esteban C, Yonei-Tamura S, Tamura K, Tsukui T, de la Peña J, Sabbagh W,

Greenwald J, Choe S, Norris DP, Robertson EJ, Evans RM, Rosenfeld MG, Izpisúa Belmonte JC: Pitx2

determines left-right asymmetry of internal organs in vertebrates. Nature 394:545-551, 1998.

294. Ryoo HL, Pierrotti D, Joyce JN: Dopamine D3 receptor is decreased and D2 receptor is elevated in the

striatum of Parkinson’s disease. Mov Disord 13:788-797, 1998.

295. Sacchetti P, Mitchell TR, Granneman JG, Bannon MJ: Nurr1 enhances transcription of the human

dopamine transporter gene through a novel mechanism. J Neurochem 76:1565-1572, 2001.

296. Sadikot AF, Luk KC, Van den Munckhof P, Rymar VV, Leung K, Gandhi R, Drouin J: Pitx3 is necessary for

survival of midbrain dopaminergic neuron subsets relevant to Parkinson’s disease. In: Bolam JP, Ingham

CA, Magill PJ (eds) Advances in Behavioral Biology 56, The Basal Ganglia VIII, 265-274, Springer, New York,

2005.

297. Sadikot AF and Sasseville R: Neurogenesis in the mammalian neostriatum and nucleus accumbens:

parvalbumin-immunoreactive GABAergic interneurons. J Comp Neurol 389:193-211, 1997.

298. Sakurada K, Ohshima-Sakurada M, Palmer TD, Gage FH: Nurr1, an orphan nuclear receptor, is a

transcriptional activator of endogenous tyrosine hydroxylase in neural progenitor cells derived from the

adult brain. Development 126:4017-4026, 1999.

299. Sala G, Brighina L, Saracchi E, Fermi S, Riva C, Carrozza V, Pirovano M, Ferrarese C: Vesicular monoamine

transporter 2 mRNA levens are reduced in platelets from patients with Parkinson’s disease. J Neural

Transm 117:1093-1098, 2010.

300. Saucedo-Cardenas O, Conneely OM: Comprative distribution of NURR1 and NURR77 nuclear receptors in

the mouse central nervous system. J Mol Neurosci 7:51-63, 1996.

301. Saucedo-Cardenas O, Quintana-Hau JD, Le WD, Smidt MP, Cox JJ, DeMayo F, Burbach JP, Conneely OM:

Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral

mesencephalic late dopaminergic precursor neurons. Proc Natl Acad Sci USA 31:4013-4018, 1998.

Appendices

150

302. Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi

M, Pecker I, Frydman M, Harnik R, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal O,

Lavin MF, Jaspers NG, Taylor AM, Arlett CF, Miki T, Weissman SM, Lovett M, Collins FS, Shiloh Y: A single

ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268:1749-1753, 1995.

303. Sayer RJ: Intracellular Ca2+ handling. Adv Exp Med Biol 513:183-196, 2002.

304. Schmidt MJ, Sawyer BD, Perry KW, Fuller RW, Foreman MM, Ghetti B: Dopamine deficiency in the weaver

mutant mouse. J Neurosci 2:376-380, 1982.

305. Schultz W: Dopamine neurons and their role in reward mechanisms. Curr Opin Neurobiol 7:191-197, 1997.

306. Schwarz M, Alvarez-Bolado G, Dressler G, Urbánek P, Busslinger M, Gruss P: Pax2/5 and Pax6 subdivide

the early neural tube into three domains. Mech Dev 82:29-39, 1999.

307. Semina EV, Ferrell RE, Mintz-Hittner HA, Bitoun P, Alward WL, Reiter RS, Funkhauser C, Daack-Hirsch S,

Murray JC: A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataract and

ASMD. Nat Genet 19:167-170, 1998.

308. Semina EV, Murray JC, Reiter R, Hrstka RF, Graw J: Deletion in the promoter region and altered expression

of Pitx3 homeobox gene in aphakia mice. Hum Mol Genet 9:1575-1585, 2000.

309. Semina EV, Reiter R, Leysens NJ, Alward WL, Small KW, Datson NA, Siegel-Bartelt J, Bierke-Nelson D,

Bitoun P, Zabel BU, Carey JC, Murray JC: Cloning and characterization of a novel bicoid-related homeobox

transcription factor gene, RIEG, involved in Rieger syndrome. Nat Genet 14:392-399, 1996.

310. Semina EV, Reiter RS, Murray JC: Isolation of a new homeobox gene belonging to the Pitx/Rieg family:

expression during lens development and mapping to the aphakia region on mouse chromosome 19. Hum

Mol Genet 6:2109-2116, 1997.

311. Sgadò P, Alberti L, Gherbassi D, Galasso SL, Ramakers GM, Alavian KN, Smidt MP, Dyck RH, Simon HH: Slow

progressive degeneration of nigral dopaminergic neurons in postnatal Engrailed mutant mice. Proc Natl

Acad Sci USA 103:15242-15247, 2006.

312. Shimoji M, Zhang L, Mandir AS, Dawson VL, Daswon TM: Absence of inclusion body formation in the MPTP

mouse model of Parkinson’s disease. Brain Res Mol Brain Res 134:103-108, 2005.

313. Sidman RL, Green MC, Appel SH: Catalog of the neurological mutants of the mouse. Harvard University

Press, Cambridge, Massachusetts, 1965.

314. Simeone A: Positioning the isthmic organizer where Otx2 and Gbx2 meet. Trends Genet 16:237-240, 2000.

315. Simon HH, Saueressig H, Wurst W, Goulding MD, O’Leary DD: Fate of midbrain dopaminergic neurons

controlled by the engrailed genes. J Neurosci 21:3126-3134, 2001.

316. Simon HH, Sgado P, Alavian KN, Alberi L, Gherbassi D, Dyck RH: The role of the engrailed transcription

factors in the survival of mesencephalic dopaminergic neurons. Mov Dis 21:S5-S6, 2006.

317. Singh B, Wilson JH, Vasavada HH, Guo Z, Allore HG, Zeis CJ: Motor deficits and altered striatal gene

expression in aphakia (ak) mice. Brain Res 118:283-292, 2007.

318. Sirinathsinghji DJS, Dunnett SB: Disappearance of the mu-opiate receptor patches in the rat neostriatum

following lesioning of the ipsilateral nigrostriatal dopamine pathway with 1-methyl-4-phenylpyridinium

ion (MPP+): restoration by embryonic nigral dopamine grafts. Brain Res 504:115-120, 1989.

319. Sivam SP: Dopamine dependent decrease in enkephalin and substance P levels in basal ganglia regions of

post-mortem Parkinson’s disease. Neuropeptides 18:201-207, 1991.

320. Smidt MP, Asbreuk CH, Cox JJ, Chen H, Johnson RL, Burbach JP: A second independent pathway for

development of mesencephalic dopaminergic neurons requires Lmx1b. Nat Neurosci 3:337-341, 2000.

321. Smidt MP, Smits SM, Bouwmeester H, Hamers FP, Van der Linden AJ, Hellemons AJ, Graw J, Burbach JP:

Early developmental failure of substantia nigra dopamine neurons in mice lacking the homeodomain gene

Pitx3. Development 131:1145-1155, 2004.

322. Smidt MP, Van Schaick HAS, Lanctôt C, Tremblay JJ, Cox JJ, Van der Kleij AAM, Wolterink G, Drouin J,

Burbach PH: A homeodomain gene PTX3 has highly restricted brain expression in mesencephalic

dopaminergic neurons. Proc Natl Acad Scie USA 94:13305-13310, 1997.

References

151

323. Smits SM, Mathon DS, Burbach JPH, Ramakers GMJ, Smidt MP: Molecular and cellular alterations in the

Pitx3-deficient midbrain dopaminergic system. Mol Cell Neurosci 30:352-363, 2005.

324. Smits SM, Noorlander CW, Kas MJH, Ramakers GMJ, Smidt MP: Alterations in serotonin signalling are

involved in the hyperactivy of Pitx3-deficient mice. Eur J Neurosci 27:388-395, 2008.

325. Snyder-Keller AM: Development of striatal compartmentalization following pre- or postnatal dopamine

depletion. J Neurosci 11:810-821, 1991.

326. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M: Alpha-synuclein in Lewy bodies.

Nature 388:839-840, 1997.

327. St Hilaire M, Landry E, Levesque D, Rouillard C: Denervation and repeated L-DOPA induce a coordinate

expression of the transcription factor NGFI-B in striatal projection pathways in hemi-parkinsonian rats.

Neurobiol Dis 14:98-109, 2003.

328. St Hilaire M, Tremblay PO, Levesque D, Barden N, Rouillard C: Effects of cocaine on c-fos and NGFI-B

mRNA expression in transgenic mice underexpressing glucocorticoid receptors.

Neuropsychopharmacology 28:478-489, 2003.

329. Ste-Marie L, Vachon L, Bemeur C, Lambert J, Montgomery J: Local striatal infusion of MPP+ does not result

in increased hydroxylation after systemic administration of 4-hydroxybenzoate. Free Radic Biol Med

27:997-1007, 1999.

330. Sveinbjornsdottir S, Hicks AA, Jonsson T, Petursson H, Gugmundsson G, Frigge ML, Kong A, Gulcher JR,

Stefansson K: Familial aggregation of Parkinson's disease in Iceland. N Engl J Med 343:1765-1770, 2000.

331. Swanson JM, Flodman P, Kennedy J, Spence MA, Moyzis R, Schuck S, Murias M, Moriarity J, Barr C, Smith

M, Posner M: Dopamine genes and ADHD. Neurol Biobehav Rev 24:21-25, 2000.

332. Swanson DJ, Zellmer E, Lewis EJ: AP1 proteins mediate the cAMP response of the dopamine beta-

hydroxylase gene. J Biol Chem 273:24065-24074, 1998.

333. Tanner CM, Ottman R, Goldman SM, Ellenberg J, Chan P, Mayeux R, Langston JW: Parkinson disease in

twins: an etiologic study. JAMA 281:341-346, 1999.

334. Taquet H, Javoy-Agid F, Giraud P, Legrand JC, Agid Y, Cesselin F: Dynorphin levels in parkinsonian patients:

Leu5-enkephalin production from either proenkephalin A or prodynorphin in human brain. Brain Res

341:390-392, 1985.

335. Taquet H, Javoy-Agid F, Hamon M, Legrand JC, Agid Y, Cesselin F: Parkinson’s disease affects differently

Met5 and Leu5-enkephalin in the human brain. Brain Res 280:379-382, 1983.

336. Thomas KR, Capecchi MR: Targeted disruption of the murine int-1 proto-oncogene resulting in severe

abnormalities in midbrain and cerebellar development. Nature 346:847-850, 1990.

337. Thornburg JE, Moore KE: Supersensitivity to dopamine agonists following unilateral 6-hydroxydopamine

induces striatal lesions in mice. J Pharmacol Exp Ther 192:42-49, 1975.

338. Tornqvist N, Hermanson E, Perlmann T, Stromberg I: Generation of tyrosine hydroxylase-immunoreactive

neurons in ventral mesencephalic tissue of Nurr1 deficient mice. Brain Res Dev Brain Res 133:37-47, 2002.

339. Torres M, Gomez-Pardo E, Gruss P: Pax2 contributes to inner ear patterning and optic nerve trajectory.

Development 122:3381-3391, 1996.

340. Tremblay JJ, Lanctôt C, Drouin J: The pan-pituitary activator of transcription, Ptx1 (pituitary homeobox 1),

acts in synergy with SF-1 and Pit1 and is an upstream regulator of the Lim-homeodomain gene Lim3/Lhx3.

Mol Endocrinol 12:428-441, 1998.

341. Triarhou LC, Norton J, Ghetti B: Mesencephalic dopamine cell deficit involves areas A8, A9 and A10 in

weaver mutant mice. Exp Brain Res 70:256-265, 1988.

342. Triarhou LC, Norton J, Hingtgen JN: Amelioration of the behavioural phenotype in weaver mutant mice

through intrastriatal grafting of fetal dopamine cells. Exp Brain Res 104:191-198, 1995.

343. Tvrdik P, Asadi A, Kozak LP, Nedergaard J, Cannon B, Jacobsson A: Cig30, a mouse member of a novel

membrane protein gene family, is involved in the recruitment of brown adipose tissue. J.Biol.Chem.

272:31738-31746, 1997.

Appendices

152

344. Ungerstedt U, Arbothnott GW: Quantitative recording of rotational behavior in rats after 6-

hydroxydopamine lesions of the nigrostriatal dopamine system. Brain Res 24:485-493, 1970.

345. Urbánek P, Wang ZQ, Fetka I, Wagner EF, Busslinger M: Complete Block of early B cell differentiation and

altered patterning of the posterior midbrain in mice lacking Pax5/BSAP. Cell 79:901-912, 1994.

346. Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio

AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP,

Lachman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW: Hereditary early-onset Parkinson’s disease

caused by mutations in PINK1. Science 304:1158-1160, 2004.

347. Valente EM, Bentivoglio AR, Dixon PH, Ferraris A, Ialongo T, Frontali M, Albanese A, Wood NW:

Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human

chromosome 1p35-p36. Am J Hum Genet 68:895-900, 2001.

348. Valente EM, Brancati F, Ferraris A, Graham EA, Davis MB, Breteler MM, Gasser T, Bonifati V, Bentivoglio

AR, De Michele G, Dürr A, Cortelli P, Wassilowsky D, Harhangi BS, Rawal N, Caputo V, Filla A, Meco G,

Oostra BA, Brice A, Albanese A, Dallapiccola B, Wood NW: Park6-linked parkinsonism occurs in several

European families. Ann Neurol 51:14-18, 2002.

349. Valente EM, Salvi S, Ialongo T, Marongiu R, Elia AE, Caputo V, Romito L, Albanese A, Dallapiccola B,

Bentivoglio AR: PINK1 mutations are associated with sporadic early-onset parkinsonism. Ann Neurol

56:336-341, 2004.

350. Van den Munckhof P, Gilbert F, Chamberland M, Levesque D, Drouin J: Striatal neuroadaptation and

rescue of locomotor deficit by L-dopa in aphakia mice, a model of Parkinson's disease. J Neurochem

96:160-170, 2006.

351. Van den Munckhof P, Luk KC, Ste-Marie L, Montgomery J, Blanchet PJ, Sadikot AF, Drouin J: Pitx3 is

required for motor activity and for survival of a subset of midbrain dopaminergic neurons. Development

130:2535-2542, 2003.

352. Van den Munckhof P, Rymar VV, Luk KC, Gu L, Weiss NS, Voorn P, Sadikot AF: Morphogenesis of rodent

neostriatum following early developmental dopamine depletion. In: Groenewegen HJ, Voorn P, Berendse

HW, Mulder AB, Cools AR (eds) Advances in Behavioral Biology 58, The Basal Ganglia IX, 399-410, Springer,

New York, 2009.

353. Van der Kooy D: Developmental relationships between opiate receptors and dopamine in the formation of

caudate-putamen patches. Brain Res Dev Brain Res 14:300-303, 1984.

354. Van der Kooy D: Early postnatal lesions of the substantia nigra produce massive shrinkage of the rat

striatum, disruption of patch neuron distribution, but no loss of patch neurons. Brain Res Dev Brain Res

94:242-245, 1996.

355. Van der Kooy D and Fishell G: Neuronal birthdate underlies the development of striatal compartments.

Brain Res 401:155-161, 1987.

356. Van der Kooy D and Fishell G: Embryonic lesions of the substantia nigra prevent the patchy expression of

opiate receptors, but not the segregation of patch and matrix compartment neurons, in the developing

striatum. Brain Res Dev Brain Res 66:141-145, 1992.

357. Van Oosten RV, Verheij MM, Cools AR: Bilateral nigral 6-hydroxydopamine lesions increase the amount of

extracellular dopamine in the nucleus accumbens. Exp Neurol 191:24-32, 2005.

358. Varnum DS, Stevens LC: Aphakia, a new mutation in the mouse. J Hered 59:147-150, 1968.

359. Vitalis T, Cases O, Engelkamp D, Verney C, Price DJ: Defects of tyrosine hydroxylase-immunoreactive

neurons in the brains of mice lacking the transcription factor Pax6. J Neurosci 20:6501-6516, 2000.

360. Wakamatsu M, Ishii A, Iwata S, Sakagami J, Ukai Y, Ono M, Kanbe D, Muramatsu S-I, Kobayashi K, Iwatsubo

T, Yoshimoto M: Selective loss of nigra dopamine neurons induced by overexpression of truncated human

α-synuclein in mice. Neurobiol Aging 29:574-585, 2008.

361. Wallén A, Zetterström RH, Solomin L, Arvidsson M, Olsen L, Perlmann T: Fate of mesencephalic AHD2-

expressing dopamine progenitor cells in NURR1 mutant mice. Exp Cell Res 253:737-746, 1999.

References

153

362. Wang H, Moriwaki A, Wang JB, Uhl GR, Pickel VM: Ultrastructural immunocytochemical localization of mu

opioid receptors and Leu5-enkephalin in the patch compartment of the rat caudate-putamen nucleus. J

Comp Neurol 375:659-674, 1996.

363. Wang YM, Gainetdinov RR, Fumagalli F, Xu F, Jones SR, Bock CB, Miller GW, Wightman RM, Caron MG:

Knockout of the vesicular monoamine transporter 2 gene results in neonatal death and supersensitivity to

cocaine and amphetamine. Neuron 19:1285-1296, 1997.

364. Wassarman KM, Lewandoski M, Campbell K, Joyner AL, Rubenstein JL, Martinez S, Martin GR: Specification

of the anterior hindbrain and establishment of a normal mid/hindbrain organizer is dependent on Gbx2

gene function. Development 124:2923-2934, 1997.

365. West MJ: New stereological methods for counting neurons. Neurobiol Aging 14:275-285, 1993.

366. West MJ, Gundersen HJ: Unbiased stereological estimation of the number of neurons in the human

hippocampus. J Comp Neurol 296:1-22, 1990.

367. Wichmann T, DeLong MR: Functional and pathophysiological models of the basal ganglia. Curr Opin

Neurobiol 6:751-758, 1997.

368. Wintermeyer P, Kruger R, Kuhn W, Muller T, Woitalla D, Berg D, Becker G, Leroy E, Polymeropoulos M,

Berger K, Przuntek H, Schols L, Epplen JT, Riess O: Mutation analysis and association studies of the UCHL1

gene in German Parkinson’s disease patients. Neuroreport 11:2079-2082, 2000.

369. Wise RA: The role of reward pathways in the developmental of drug dependence. Pharmacol ther 35:227-

263, 1987.

370. Witta J, Baffi JS, Palkovits M, Mezey E, Castillo SO, Nikodem VM: Nigrostriatal innervation is preserved in

Nurr1-null mice, although dopaminergic neuron precursors are arrested from terminal differentiation.

Bran Res Mol Brain Res 84:67-78, 2000.

371. Wurst W, Auerbach AB, Joyner AL: Multiple developmental defects in Engrailed-1 mutant mice: an early

mid-hindbrain deletion and patterning defects in forelimbs and sternum. Development 120:2065-2075,

1994.

372. Xiao Q, Castillo SO, Nikodem VM: Distribution of messenger RNAs for the orphan nuclear receptors Nurr1

and Nurr77 (NGFI-B) in adult rat brain using in situ hybridization. Neuroscience 75:221-230, 1996.

373. Xu M, Moratalla R, Gold LH, Hiroi N, Koob GF, Graybiel AM, Tonegawa S: Dopamine D1 receptor mutant

mice are deficient in striatal expression of dynorphin and in dopamine-mediated behavioral responses.

Cell 79:729-742, 1994.

374. Xu PY, Liang R, Jankovic J, Hunter C, Zeng YX, Ashizawa T, Lai D, Le WD: Association of homozygous

7048G7049 variant in the intron six of Nurr1 gene with Parkinson’s disease. Neurology 58:881-884, 2002.

375. Yamada T, McGeer PL, Baimbridge KG, McGeer EG: Relative sparing in Parkinson’s disease of substantia

nigra dopamine neurons containing calbindin-D28K. Brain Res 526:303-307, 1990.

376. Ye W, Shimamura K, Rubinstein JL, Hynes MA, Rosenthal A: FGF and Shh signals control dopaminergic and

serotonergic cell faite in the anterior neural plate. Cell 93:755-766, 1998.

377. Yu LH, Lin ZF, Hu FY, He XH, Liu ZL, Xu YM: The transcription factor Pitx3 is a risk modifier for Parkinson’s

disease in a Chinese Han population. Eur J Neurol Epub ahead of print, 2010.

378. Zabetian CP, Samii A, Mosley AD, Roberts JW, Leis BC, Yearout D, Raskind WH, Griffith: A clinic-based study

of the LRRK2 gene in Parkinson disease yields new mutations. Neurology 65:741-744, 2005.

379. Zarow C, Lyness SA, Mortimer JA, Chui HC: Neuronal loss is greater in the locus coeruleus than nucleus

basalis and substantia nigra in Alzheimer and Parkinson’s disease. Arch Neurol 60:337-341, 2003.

380. Zarranz JJ, Alegre J, Gomez-Esteban JC, Lezcano E, Ros R, Ampuero I, Vidal L, Hoenicka J, Rodriguez O,

Atares B, Llorens V, Gomez Tortosa E, del Ser T, Munoz DG, de Yebenes JG: The new mutation, E46K, of

alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 55:164-173, 2004.

381. Zetterström RH, Solomin L, Jansson L, Hoffer BJ, Olson L, Perlmann T: Dopamine neuron agenesis in Nurr1-

deficient mice. Science 276:248-250, 1997.

Appendices

154

382. Zetterström RH, Williams R, Perlmann T, Olson L: Cellular expression of the immediate early transcription

factors Nurr1 and NGFI-B suggests a gene regulatory role in several brain regions including the

nigrostriatal dopamine system. Brain Res Mol Brain Res 41:111-120, 1996.

383. Zhao SL, Maxwell S, Jimenez-Beristain A, Vives J, Kuehner E, Zhao JX, O'Brien C, de Felipe C, Semina E, Li M:

Generation of embryonic stem cells and transgenic mice expressing green fluorescence protein in

midbrain dopaminergic neurons. Eur J Neurosci 19:1133-1140, 2004.

384. Zheng B, Albrecht U, Kaasik K, Sage M, Lu W, Vaishnav S, Li Q, Sun ZS, Eichele G, Bradley A, Lee CC:

Nonredundant roles of the mPer1 and mPer2 genes in the mammalian circadian clock. Cell 105:683-694,

2001.

385. Zhou QY, Palmiter RD: Dopamine-deficient mice are severly hypoactive, adipsic, and aphagic. Cell 83:1197-

1209, 1995.

386. Zhuang X, Masson J, Gingrich JA, Rayport S, Hen R: Targeted gene expression in dopamine and serotonin

neurons of the mouse brain. J Neurosci Methods 143:27-32, 2005.

387. Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB,

Stoessl AL, Pfeiffer RF, Patenge N, Carbajal IC, Vieregge P, Asmus F, Müller-Myhsok B, Dickson DW,

Meitinger T, Strom TM, Wszolek ZK, Gasser T: Mutationa in LRRK2 cause autosomal-dominant

parkinsonism with pleomorphic pathology. Neuron 44:601-607, 2004.