Genetically engineered mouse models of the trinucleotide-repeat spinocerebellar ataxias

Brain Research Bulletin

Volumn 88, Issue 1, 2012, Pages 33-42

  Ingram, Melissa A C ^a   Orr, Harry T ^a   Clark, H Brent ^a  

^a UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

Author keywords

Purkinje cell; Spinocerebellar ataxia; Transgenic mice; Trinucleotide repeat disease

Indexed keywords

MUTANT PROTEIN; POLYGLUTAMINE;

ANIMAL MODEL; BRAIN FUNCTION; GENE CONTROL; GENE MUTATION; GENETIC ENGINEERING; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN LOCALIZATION; REVIEW; SPINOCEREBELLAR DEGENERATION; TRINUCLEOTIDE REPEAT;

ANIMALS; DISEASE MODELS, ANIMAL; GENETIC ENGINEERING; HUMANS; MICE; MICE, NEUROLOGIC MUTANTS; PEPTIDES; SPINOCEREBELLAR ATAXIAS; TRINUCLEOTIDE REPEAT EXPANSION;

EID: 84860455844     PISSN: 03619230     EISSN: 18732747     Source Type: Journal    
DOI: 10.1016/j.brainresbull.2011.07.016     Document Type: Review

References (102)

1. Abeliovich A., Chen C., Goda Y., Silva A.J., Stevens C.F., Tonegawa S. Modified hippocampal long-term potentiation in PKC gamma-mutant mice. Cell 1993, 75:1253-1262.
2. Abou-Sleymane G., Chalmel F., Helmlinger D., Lardenois A., Thibault C., Weber C., Merienne K., Mandel J.L., Poch O., Devys D., Trottier Y. Polyglutamine expansion causes neurodegeneration by altering the neuronal differentiation program. Hum. Mol. Genet. 2006, 15:691-703.
3. Aguiar J., Fernandez J., Aguilar A., Mendoza Y., Vazquez M., Suarez J., Berlanga J., Cruz S., Guillen G., Herrera L., Velazquez L., Santos N., Merino N. Ubiquitous expression of human SCA2 gene under the regulation of the SCA2 self promoter cause specific Purkinje cell degeneration in transgenic mice. Neurosci. Lett. 2006, 392:202-206.
4. Banfi S., Servadio A., Chung M.Y., Kwiatkowski T.J., McCall A.E., Duvick L.A., Shen Y., Roth E.J., Orr H.T., Zoghbi H.Y. Identification and characterization of the gene causing type 1 spinocerebellar ataxia. Nat. Genet. 1994, 7:513-520.
5. Bichelmeier U., Schmidt T., Hubener J., Boy J., Ruttiger L., Habig K., Poths S., Bonin M., Knipper M., Schmidt W.J., Wilbertz J., Wolburg H., Laccone F., Riess O. Nuclear localization of ataxin-3 is required for the manifestation of symptoms in SCA3: in vivo evidence. J. Neurosci. 2007, 27:7418-7428.
6. Borchelt D.R., Davis J., Fischer M., Lee M.K., Slunt H.H., Ratovitsky T., Regard J., Copeland N.G., Jenkins N.A., Sisodia S.S., Price D.L. A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet. Anal. 1996, 13:159-163.
7. Bowman A.B., Lam Y.C., Jafar-Nejad P., Chen H.K., Richman R., Samaco R.C., Fryer J.D., Kahle J.J., Orr H.T., Zoghbi H.Y. Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing incorporation of polyglutamine-expanded ataxin-1 into native complexes. Nat. Genet. 2007, 39:373-379.
8. Bowman A.B., Yoo S.Y., Dantuma N.P., Zoghbi H.Y. Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin-proteasome system impairment and inversely correlates with the degree of nuclear inclusion formation. Hum. Mol. Genet. 2005, 14:679-691.
9. Boy J., Schmidt T., Schumann U., Grasshoff U., Unser S., Holzmann C., Schmitt I., Karl T., Laccone F., Wolburg H., Ibrahim S., Riess O. A transgenic mouse model of spinocerebellar ataxia type 3 resembling late disease onset and gender-specific instability of CAG repeats. Neurobiol. Dis. 2010, 37:284-293.
10. Boy J., Schmidt T., Wolburg H., Mack A., Nuber S., Bottcher M., Schmitt I., Holzmann C., Zimmermann F., Servadio A., Riess O. Reversibility of symptoms in a conditional mouse model of spinocerebellar ataxia type 3. Hum. Mol. Genet. 2009, 18:4282-4295.
11. Brenner M., Kisseberth W.C., Su Y., Besnard F., Messing A. GFAP promoter directs astrocyte-specific expression in transgenic mice. J. Neurosci. 1994, 14:1030-1037.
12. Bruni A.C., Takahashi-Fujigasaki J., Maltecca F., Foncin J.F., Servadio A., Casari G., D'Adamo P., Maletta R., Curcio S.A., De Michele G., Filla A., El Hachimi K.H., Duyckaerts C. Behavioral disorder, dementia, ataxia, and rigidity in a large family with TATA box-binding protein mutation. Arch. Neurol. 2004, 61:1314-1320.
13. Burright E.N., Clark H.B., Servadio A., Matilla T., Feddersen R.M., Yunis W.S., Duvick L.A., Zoghbi H.Y., Orr H.T. SCA1 transgenic mice: a model for neurodegeneration caused by an expanded CAG trinucleotide repeat. Cell 1995, 82:937-948.
14. Cemal C.K., Carroll C.J., Lawrence L., Lowrie M.B., Ruddle P., Al-Mahdawi S., King R.H., Pook M.A., Huxley C., Chamberlain S. YAC transgenic mice carrying pathological alleles of the MJD1 locus exhibit a mild and slowly progressive cerebellar deficit. Hum. Mol. Genet. 2002, 11:1075-1094.
15. Chen H.K., Fernandez-Funez P., Acevedo S.F., Lam Y.C., Kaytor M.D., Fernandez M.H., Aitken A., Skoulakis E.M., Orr H.T., Botas J., Zoghbi H.Y. Interaction of Akt-phosphorylated ataxin-1 with 14-3-3 mediates neurodegeneration in spinocerebellar ataxia type 1. Cell 2003, 113:457-468.
16. Chen X., Tang T.S., Tu H., Nelson O., Pook M., Hammer R., Nukina N., Bezprozvanny I. Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 3. J. Neurosci. 2008, 28:12713-12724.
17. Chintawar S., Hourez R., Ravella A., Gall D., Orduz D., Rai M., Bishop D.P., Geuna S., Schiffmann S.N., Pandolfo M. Grafting neural precursor cells promotes functional recovery in an SCA1 mouse model. J. Neurosci. 2009, 29:13126-13135.
18. Chou A.H., Chen C.Y., Chen S.Y., Chen W.J., Chen Y.L., Weng Y.S., Wang H.L. Polyglutamine-expanded ataxin-7 causes cerebellar dysfunction by inducing transcriptional dysregulation. Neurochem. Int. 2010, 56:329-339.
19. Chou A.H., Chen S.Y., Yeh T.H., Weng Y.H., Wang H.L. HDAC inhibitor sodium butyrate reverses transcriptional downregulation and ameliorates ataxic symptoms in a transgenic mouse model of SCA3. Neurobiol. Dis. 2011, 41:481-488.
20. Chou A.H., Yeh T.H., Ouyang P., Chen Y.L., Chen S.Y., Wang H.L. Polyglutamine-expanded ataxin-3 causes cerebellar dysfunction of SCA3 transgenic mice by inducing transcriptional dysregulation. Neurobiol. Dis. 2008, 31:89-101.
21. Clark H.B., Burright E.N., Yunis W.S., Larson S., Wilcox C., Hartman B., Matilla A., Zoghbi H.Y., Orr H.T. Purkinje cell expression of a mutant allele of SCA1 in transgenic mice leads to disparate effects on motor behaviors, followed by a progressive cerebellar dysfunction and histological alterations. J. Neurosci. 1997, 17:7385-7395.
22. Clarkson Y.L., Gillespie T., Perkins E.M., Lyndon A.R., Jackson M. Beta-III spectrin mutation L253P associated with spinocerebellar ataxia type 5 interferes with binding to Arp1 and protein trafficking from the Golgi. Hum. Mol. Genet. 2010, 19:3634-3641.
23. Colomer Gould V.F., Goti D., Pearce D., Gonzalez G.A., Gao H., Bermudez de Leon M., Jenkins N.A., Copeland N.G., Ross C.A., Brown D.R. A mutant ataxin-3 fragment results from processing at a site N-terminal to amino acid 190 in brain of Machado-Joseph disease-like transgenic mice. Neurobiol. Dis. 2007, 27:362-369.
24. Cummings C.J., Mancini M.A., Antalffy B., DeFranco D.B., Orr H.T., Zoghbi H.Y. Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1. Nat. Genet. 1998, 19:148-154.
25. Cummings C.J., Sun Y., Opal P., Antalffy B., Mestril R., Orr H.T., Dillmann W.H., Zoghbi H.Y. Over-expression of inducible HSP70 chaperone suppresses neuropathology and improves motor function in SCA1 mice. Hum. Mol. Genet. 2001, 10:1511-1518.
26. Custer S.K., Garden G.A., Gill N., Rueb U., Libby R.T., Schultz C., Guyenet S.J., Deller T., Westrum L.E., Sopher B.L., La Spada A.R. Bergmann glia expression of polyglutamine-expanded ataxin-7 produces neurodegeneration by impairing glutamate transport. Nat. Neurosci. 2006, 9:1302-1311.
27. Daughters R.S., Tuttle D.L., Gao W., Ikeda Y., Moseley M.L., Ebner T.J., Swanson M.S., Ranum L.P. RNA gain-of-function in spinocerebellar ataxia type 8. PLoS Genet. 2009, 5:e1000600.
28. David G., Abbas N., Stevanin G., Durr A., Yvert G., Cancel G., Weber C., Imbert G., Saudou F., Antoniou E., Drabkin H., Gemmill R., Giunti P., Benomar A., Wood N., Ruberg M., Agid Y., Mandel J.L., Brice A. Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat. Genet. 1997, 17:65-70.
29. Duvick L., Barnes J., Ebner B., Agrawal S., Andresen M., Lim J., Giesler G.J., Zoghbi H.Y., Orr H.T. SCA1-like disease in mice expressing wild-type ataxin-1 with a serine to aspartic acid replacement at residue 776. Neuron 2010, 67:929-935.
30. Emamian E.S., Kaytor M.D., Duvick L.A., Zu T., Tousey S.K., Zoghbi H.Y., Clark H.B., Orr H.T. Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in SCA1 transgenic mice. Neuron 2003, 38:375-387.
31. Fischer M., Rulicke T., Raeber A., Sailer A., Moser M., Oesch B., Brandner S., Aguzzi A., Weissmann C. Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie. EMBO J. 1996, 15:1255-1264.
32. Friedman M.J., Shah A.G., Fang Z.H., Ward E.G., Warren S.T., Li S., Li X.J. Polyglutamine domain modulates the TBP-TFIIB interaction: implications for its normal function and neurodegeneration. Nat. Neurosci. 2007, 10:1519-1528.
33. Friedman M.J., Wang C.E., Li X.J., Li S. Polyglutamine expansion reduces the association of TATA-binding protein with DNA and induces DNA binding-independent neurotoxicity. J. Biol. Chem. 2008, 283:8283-8290.
34. Garden G.A., Libby R.T., Fu Y.H., Kinoshita Y., Huang J., Possin D.E., Smith A.C., Martinez R.A., Fine G.C., Grote S.K., Ware C.B., Einum D.D., Morrison R.S., Ptacek L.J., Sopher B.L., La Spada A.R. Polyglutamine-expanded ataxin-7 promotes non-cell-autonomous purkinje cell degeneration and displays proteolytic cleavage in ataxic transgenic mice. J. Neurosci. 2002, 22:4897-4905.
35. Gatchel J.R., Watase K., Thaller C., Carson J.P., Jafar-Nejad P., Shaw C., Zu T., Orr H.T., Zoghbi H.Y. The insulin-like growth factor pathway is altered in spinocerebellar ataxia type 1 and type 7. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:1291-1296.
36. Gehrking K.M., Andresen J.M., Duvick L., Lough J., Zoghbi H.Y., Orr H.T. Partial loss of Tip60 slows mid-stage neurodegeneration in a spinocerebellar ataxia type 1 (SCA1) mouse model. Hum. Mol. Genet. 2011, 20:2204-2212.
37. Giovannoni R., Maggio N., Rosaria Bianco M., Cavaliere C., Cirillo G., Lavitrano M., Papa M. Reactive astrocytosis and glial glutamate transporter clustering are early changes in a spinocerebellar ataxia type 1 transgenic mouse model. Neuron Glia Biol. 2007, 3:335-351.
38. Goti D., Katzen S.M., Mez J., Kurtis N., Kiluk J., Ben-Haiem L., Jenkins N.A., Copeland N.G., Kakizuka A., Sharp A.H., Ross C.A., Mouton P.R., Colomer V. A mutant ataxin-3 putative-cleavage fragment in brains of Machado-Joseph disease patients and transgenic mice is cytotoxic above a critical concentration. J. Neurosci. 2004, 24:10266-10279.
39. Griffin J.L., Cemal C.K., Pook M.A. Defining a metabolic phenotype in the brain of a transgenic mouse model of spinocerebellar ataxia 3. Physiol. Genomics 2004, 16:334-340.
40. He Y., Zu T., Benzow K.A., Orr H.T., Clark H.B., Koob M.D. Targeted deletion of a single Sca8 ataxia locus allele in mice causes abnormal gait, progressive loss of motor coordination, and Purkinje cell dendritic deficits. J. Neurosci. 2006, 26:9975-9982.
41. Helmlinger D., Hardy S., Abou-Sleymane G., Eberlin A., Bowman A.B., Gansmuller A., Picaud S., Zoghbi H.Y., Trottier Y., Tora L., Devys D. Glutamine-expanded ataxin-7 alters TFTC/STAGA recruitment and chromatin structure leading to photoreceptor dysfunction. PLoS Biol. 2006, 4:e67.
42. Helmlinger D., Hardy S., Sasorith S., Klein F., Robert F., Weber C., Miguet L., Potier N., Van-Dorsselaer A., Wurtz J.M., Mandel J.L., Tora L., Devys D. Ataxin-7 is a subunit of GCN5 histone acetyltransferase-containing complexes. Hum. Mol. Genet. 2004, 13:1257-1265.
43. Hubener J., Riess O. Polyglutamine-induced neurodegeneration in SCA3 is not mitigated by non-expanded ataxin-3: conclusions from double-transgenic mouse models. Neurobiol. Dis. 2010, 38:116-124.
44. Hurlock E.C., McMahon A., Joho R.H. Purkinje-cell-restricted restoration of Kv3.3 function restores complex spikes and rescues motor coordination in Kcnc3 mutants. J. Neurosci. 2008, 28:4640-4648.
45. Huynh D.P., Figueroa K., Hoang N., Pulst S.M. Nuclear localization or inclusion body formation of ataxin-2 are not necessary for SCA2 pathogenesis in mouse or human. Nat. Genet. 2000, 26:44-50.
46. Huynh D.P., Maalouf M., Silva A.J., Schweizer F.E., Pulst S.M. Dissociated fear and spatial learning in mice with deficiency of ataxin-2. PLoS One 2009, 4:e6235.
47. Ikeda H., Yamaguchi M., Sugai S., Aze Y., Narumiya S., Kakizuka A. Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo. Nat. Genet. 1996, 13:196-202.
48. Imbert G., Saudou F., Yvert G., Devys D., Trottier Y., Garnier J.M., Weber C., Mandel J.L., Cancel G., Abbas N., Durr A., Didierjean O., Stevanin G., Agid Y., Brice A. Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. Nat. Genet. 1996, 14:285-291.
49. Jafar-Nejad P., Ward C.S., Richman R., Orr H.T., Zoghbi H.Y. Regional rescue of spinocerebellar ataxia type 1 phenotypes by 14-3-3epsilon haploinsufficiency in mice underscores complex pathogenicity in neurodegeneration. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:2142-2147.
50. Kano M., Hashimoto K., Chen C., Abeliovich A., Aiba A., Kurihara H., Watanabe M., Inoue Y., Tonegawa S. Impaired synapse elimination during cerebellar development in PKC gamma mutant mice. Cell 1995, 83:1223-1231.
51. Kiehl T.R., Nechiporuk A., Figueroa K.P., Keating M.T., Huynh D.P., Pulst S.M. Generation and characterization of Sca2 (ataxin-2) knockout mice. Biochem. Biophys. Res. Commun. 2006, 339:17-24.
52. Klement I.A., Skinner P.J., Kaytor M.D., Yi H., Hersch S.M., Clark H.B., Zoghbi H.Y., Orr H.T. Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice. Cell 1998, 95:41-53.
53. Koob M.D., Moseley M.L., Schut L.J., Benzow K.A., Bird T.D., Day J.W., Ranum L.P. An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat. Genet. 1999, 21:379-384.
54. Koob M.D., Moseley M.L., Schut L.J., et al. An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat. Genet. 1999, 379-384.
55. La Spada A.R., Fu Y.H., Sopher B.L., Libby R.T., Wang X., Li L.Y., Einum D.D., Huang J., Possin D.E., Smith A.C., Martinez R.A., Koszdin K.L., Treuting P.M., Ware C.B., Hurley J.B., Ptacek L.J., Chen S. Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7. Neuron 2001, 31:913-927.
56. + channels and impairs neuronal excitability. J. Neurosci. 2007, 27:12033-12044.
57. Lim J., Crespo-Barreto J., Jafar-Nejad P., Bowman A.B., Richman R., Hill D.E., Orr H.T., Zoghbi H.Y. Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1. Nature 2008, 452:713-718.
58. Liu J., Tang T.S., Tu H., Nelson O., Herndon E., Huynh D.P., Pulst S.M., Bezprozvanny I. Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 2. J. Neurosci. 2009, 29:9148-9162.
59. Lorenzetti D., Watase K., Xu B., Matzuk M.M., Orr H.T., Zoghbi H.Y. Repeat instability and motor incoordination in mice with a targeted expanded CAG repeat in the Sca1 locus. Hum. Mol. Genet. 2000, 9:779-785.
60. Matilla A., Roberson E.D., Banfi S., Morales J., Armstrong D.L., Burright E.N., Orr H.T., Sweatt J.D., Zoghbi H.Y., Matzuk M.M. Mice lacking ataxin-1 display learning deficits and decreased hippocampal paired-pulse facilitation. J. Neurosci. 1998, 18:5508-5516.
61. Menzies F.M., Huebener J., Renna M., Bonin M., Riess O., Rubinsztein D.C. Autophagy induction reduces mutant ataxin-3 levels and toxicity in a mouse model of spinocerebellar ataxia type 3. Brain 2010, 133:93-104.
62. Merienne K., Friedman J., Akimoto M., Abou-Sleymane G., Weber C., Swaroop A., Trottier Y. Preventing polyglutamine-induced activation of c-Jun delays neuronal dysfunction in a mouse model of SCA7 retinopathy. Neurobiol. Dis. 2007, 25:571-581.
63. Moseley M.L., Zu T., Ikeda Y., Gao W., Mosemiller A.K., Daughters R.S., Chen G., Weatherspoon M.R., Clark H.B., Ebner T.J., Day J.W., Ranum L.P. Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8. Nat. Genet. 2006, 38:758-769.
64. Nakamura K., Jeong S.Y., Uchihara T., Anno M., Nagashima K., Nagashima T., Ikeda S., Tsuji S., Kanazawa I. SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum. Mol. Genet. 2001, 10:1441-1448.
65. Oberdick J., Smeyne R.J., Mann J.R., Zackson S., Morgan J.I. A promoter that drives transgene expression in cerebellar Purkinje and retinal bipolar neurons. Science 1990, 248:223-226.
66. Orr H.T., Chung M.Y., Banfi S., Kwiatkowski T.J., Servadio A., Beaudet A.L., McCall A.E., Duvick L.A., Ranum L.P., Zoghbi H.Y. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat. Genet. 1993, 4:221-226.
67. Oz G., Hutter D., Tkac I., Clark H.B., Gross M.D., Jiang H., Eberly L.E., Bushara K.O., Gomez C.M. Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status. Mov. Disord. 2010, 25:1253-1261.
68. Oz G., Nelson C.D., Koski D.M., Henry P.G., Marjanska M., Deelchand D.K., Shanley R., Eberly L.E., Orr H.T., Clark H.B. Noninvasive detection of presymptomatic and progressive neurodegeneration in a mouse model of spinocerebellar ataxia type 1. J. Neurosci. 2010, 30:3831-3838.
69. Paciokowski A.R., Shafrir Y., Hrivnak J., Patterson M.C., Tennison M.B., Clark H.B., Dobyns W.B., Gomez C.M. Massive expansion of SCA2: a progressive encephalopathy with infantile spasms, retinitis pigmentosa, and autonomic dysfunction. Neurology 2011, 17.
70. Perkins E.M., Clarkson Y.L., Sabatier N., Longhurst D.M., Millward C.P., Jack J., Toraiwa J., Watanabe M., Rothstein J.D., Lyndon A.R., Wyllie D.J., Dutia M.B., Jackson M. Loss of beta-III spectrin leads to Purkinje cell dysfunction recapitulating the behavior and neuropathology of spinocerebellar ataxia type 5 in humans. J. Neurosci. 2010, 30:4857-4867.
71. Pulst S.M., Nechiporuk A., Nechiporuk T., Gispert S., Chen X.N., Lopes-Cendes I., Pearlman S., Starkman S., Orozco-Diaz G., Lunkes A., DeJong P., Rouleau G.A., Auburger G., Korenberg J.R., Figueroa C., Sahba S. Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2. Nat. Genet. 1996, 14:269-276.
72. Qin Q., Inatome R., Hotta A., Kojima M., Yamamura H., Hirai H., Yoshizawa T., Tanaka H., Fukami K., Yanagi S. A novel GTPase, CRAG, mediates promyelocytic leukemia protein-associated nuclear body formation and degradation of expanded polyglutamine protein. J. Cell Biol. 2006, 172:497-504.
73. Ross C.A. Intranuclear neuronal inclusions: a common pathogenic mechanism for glutamine-repeat neurodegenerative diseases?. Neuron 1997, 19:1147-1150.
74. Saegusa H., Wakamori M., Matsuda Y., Wang J., Mori Y., Zong S., Tanabe T. Properties of human Cav2.1 channel with a spinocerebellar ataxia type 6 mutation expressed in Purkinje cells. Mol. Cell. Neurosci. 2007, 34:261-270.
75. Sanpei K., Takano H., Igarashi S., Sato T., Oyake M., Sasaki H., Wakisaka A., Tashiro K., Ishida Y., Ikeuchi T., Koide R., Saito M., Sato A., Tanaka T., Hanyu S., Takiyama Y., Nishizawa M., Shimizu N., Nomura Y., Segawa M., Iwabuchi K., Eguchi I., Tanaka H., Takahashi H., Tsuji S. Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT. Nat. Genet. 1996, 14:277-284.
76. Schmitt I., Linden M., Khazneh H., Evert B.O., Breuer P., Klockgether T., Wuellner U. Inactivation of the mouse Atxn3 (ataxin-3) gene increases protein ubiquitination. Biochem. Biophys. Res. Commun. 2007, 362:734-739.
77. Serra H.G., Duvick L., Zu T., Carlson K., Stevens S., Jorgensen N., Lysholm A., Burright E., Zoghbi H.Y., Clark H.B., Andresen J.M., Orr H.T. RORalpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice. Cell 2006, 127:697-708.
78. Servadio A., Koshy B., Armstrong D., Antalffy B., Orr H.T., Zoghbi H.Y. Expression analysis of the ataxin-1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals. Nat. Genet. 1995, 10:94-98.
79. Shah A.G., Friedman M.J., Huang S., Roberts M., Li X.J., Li S. Transcriptional dysregulation of TrkA associates with neurodegeneration in spinocerebellar ataxia type 17. Hum. Mol. Genet. 2009, 18:4141-4152.
80. Shakkottai V.G., Xiao M., Xu L., Wong M., Nerbonne J.M., Ornitz D.M., Yamada K.A. FGF14 regulates the intrinsic excitability of cerebellar Purkinje neurons. Neurobiol. Dis. 2009, 33:81-88.
81. Silva-Fernandes A., Costa Mdo C., Duarte-Silva S., Oliveira P., Botelho C.M., Martins L., Mariz J.A., Ferreira T., Ribeiro F., Correia-Neves M., Costa C., Maciel P. Motor uncoordination and neuropathology in a transgenic mouse model of Machado-Joseph disease lacking intranuclear inclusions and ataxin-3 cleavage products. Neurobiol. Dis. 2010, 40:163-176.
82. Smeyne R.J., Oberdick J., Schilling K., Berrebi A.S., Mugnaini E., Morgan J.I. Dynamic organization of developing Purkinje cells revealed by transgene expression. Science 1991, 254:719-721.
83. Stevanin G., Le G.E., Ravise N., et al. A third locus for autosomal dominant cerebellar ataxia type I maps to chromosome 14q24.3-qter: evidence for the existence of a fourth locus. Am. J. Hum. Genet. 1994, 54:11-20.
84. Switonski P.M., Fiszer A., Kazmierska K., Kurpisz M., Krzyzosiak W.J., Figiel M. Mouse ataxin-3 functional knock-out model. Neuromol. Med. 2011, 13:54-65.
85. Torashima T., Koyama C., Iizuka A., Mitsumura K., Takayama K., Yanagi S., Oue M., Yamaguchi H., Hirai H. Lentivector-mediated rescue from cerebellar ataxia in a mouse model of spinocerebellar ataxia. EMBO Rep. 2008, 9:393-399.
86. Wang H.L., Chou A.H., Lin A.C., Chen S.Y., Weng Y.H., Yeh T.H. Polyglutamine-expanded ataxin-7 upregulates Bax expression by activating p53 in cerebellar and inferior olivary neurons. Exp. Neurol. 2010, 224:486-494.
87. Wang Q., Bardgett M.E., Wong M., Wozniak D.F., Lou J., McNeil B.D., Chen C., Nardi A., Reid D.C., Yamada K., Ornitz D.M. Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14. Neuron 2002, 35:25-38.
88. Watase K., Barrett C.F., Miyazaki T., Ishiguro T., Ishikawa K., Hu Y., Unno T., Sun Y., Kasai S., Watanabe M., Gomez C.M., Mizusawa H., Tsien R.W., Zoghbi H.Y. Spinocerebellar ataxia type 6 knockin mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant CaV2.1 channels. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:11987-11992.
89. Watase K., Gatchel J.R., Sun Y., Emamian E., Atkinson R., Richman R., Mizusawa H., Orr H.T., Shaw C., Zoghbi H.Y. Lithium therapy improves neurological function and hippocampal dendritic arborization in a spinocerebellar ataxia type 1 mouse model. PLoS Med. 2007, 4:e182.
90. Watase K., Venken K.J., Sun Y., Orr H.T., Zoghbi H.Y. Regional differences of somatic CAG repeat instability do not account for selective neuronal vulnerability in a knock-in mouse model of SCA1. Hum. Mol. Genet. 2003, 12:2789-2795.
91. Watase K., Weeber E.J., Xu B., Antalffy B., Yuva-Paylor L., Hashimoto K., Kano M., Atkinson R., Sun Y., Armstrong D.L., Sweatt J.D., Orr H.T., Paylor R., Zoghbi H.Y. A long CAG repeat in the mouse Sca1 locus replicates SCA1 features and reveals the impact of protein solubility on selective neurodegeneration. Neuron 2002, 34:905-919.
92. Waters M.F., Minassian N.A., Stevanin G., Figueroa K.P., Bannister J.P., Nolte D., Mock A.F., Evidente V.G., Fee D.B., Muller U., Durr A., Brice A., Papazian D.M., Pulst S.M. Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nat. Genet. 2006, 38:447-451.
93. Williams A.J., Knutson T.M., Colomer Gould V.F., Paulson H.L. In vivo suppression of polyglutamine neurotoxicity by C-terminus of Hsp70-interacting protein (CHIP) supports an aggregation model of pathogenesis. Neurobiol. Dis. 2009, 33:342-353.
94. Xia H., Mao Q., Eliason S.L., Harper S.Q., Martins I.H., Orr H.T., Paulson H.L., Yang L., Kotin R.M., Davidson B.L. RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat. Med. 2004, 10:816-820.
95. Yoo S.Y., Pennesi M.E., Weeber E.J., Xu B., Atkinson R., Chen S., Armstrong D.L., Wu S.M., Sweatt J.D., Zoghbi H.Y. SCA7 knockin mice model human SCA7 and reveal gradual accumulation of mutant ataxin-7 in neurons and abnormalities in short-term plasticity. Neuron 2003, 37:383-401.
96. Yvert G., Lindenberg K.S., Devys D., Helmlinger D., Landwehrmeyer G.B., Mandel J.L. SCA7 mouse models show selective stabilization of mutant ataxin-7 and similar cellular responses in different neuronal cell types. Hum. Mol. Genet. 2001, 10:1679-1692.
97. Yvert G., Lindenberg K.S., Picaud S., et al. Expanded polyglutamines induce neurodegeneration and trans-neuronal alterations in cerebellum and retina of SCA7 transgenic mice. Hum. Mol. Genet. 2000, 9:2491-2506.
98. Zhang Y., Snider A., Willard L., Takemoto D.J., Lin D. Loss of Purkinje cells in the PKCgamma H101Y transgenic mouse. Biochem. Biophys. Res. Commun. 2009, 378:524-528.
99. Zhuchenko O., Bailey J., Bonnen P., Ashizawa T., Stockton D.W., Amos C., Dobyns W.B., Subramony S.H., Zoghbi H.Y., Lee C.C. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat. Genet. 1997, 15:62-69.
100. Zoghbi H.Y., Orr H.T. Spinocerebellar ataxia type 1. Semin. Cell Biol. 1995, 6:29-35.
101. Zu T., Duvick L.A., Kaytor M.D., Berlinger M.S., Zoghbi H.Y., Clark H.B., Orr H.T. Recovery from polyglutamine-induced neurodegeneration in conditional SCA1 transgenic mice. J. Neurosci. 2004, 24:8853-8861.
102. Zu T., Gibbens B., Doty N.S., Gomes-Pereira M., Huguet A., Stone M.D., Margolis J., Peterson M., Markowski T.W., Ingram M.A., Nan Z., Forster C., Low W.C., Schoser B., Somia N.V., Clark H.B., Schmechel S., Bitterman P.B., Gourdon G., Swanson M.S., Moseley M., Ranum L.P. Non-ATG-initiated translation directed by microsatellite expansions. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:260-265.