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. Author manuscript; available in PMC: 2014 Nov 1.
Published in final edited form as: Neurol Clin. 2013 Jul 30;31(4):10.1016/j.ncl.2013.04.006. doi: 10.1016/j.ncl.2013.04.006

Table 2.

Animal models of SCA.

Name Type of modela Phenotype Pathology Selected Therapy Trials
SCA1 Transgenic-(Purkinje neuron specific), 82Q [s1] Motor incoordination Shrinkage and marked loss of Purkinje neurons shRNA [s3]
Knock-in, 154Q [s2] Cognitive impairment
Kyphosis
Motor incoordination
Premature death
Weight loss
Mild loss of Purkinje neurons Lithium [s4]
Vascular Endothelial
Growth Factor (VEGF) [s5]

SCA2 Transgenic 58Q and 127Q (Purkinje neuron specific)[s6] Motor incoordination Shrinkage and mild loss of Purkinje neurons Dantrolene [s7]
SK channel activator [s8]

SCA3 (Machado– Joseph Disease/ MJD) Transgenic (many models including 79Q[s9], 148Q [s10], 71Q [s11], 94Q [s12], 77Q [s13]) Motor incoordination Premature death Variable shrinkage and mild neuronal loss Sodium butyrate [s19]
Yeast Artificial
 Chromosome
 Transgenic [s1416]
Motor incoordination Mild and late loss of brain stem and cerebellar neurons Dantrolene [s15]
Rat model-lentiviral injection and overexpression of mutant ataxin-3 in the striatum or substantia nigra [s17] Circling behavior following unilateral substantia nigra injection Fluorojade positive neurons and cell shrinkage shRNA [s20]
Fly eye [s18] Loss of ommatidia

SCA5 Knock-out [s21] Motor incoordination Shrinkage and mild loss of Purkinje neurons

SCA6 Knock-in 84Q [s22] Motor incoordination Very mild Purkinje neuron loss

SCA7 Transgenic [s23] Motor incoordination Mild Purkinje neuron loss

SCA8 Klh1 deletion [s24] Motor incoordination Purkinje neuron shrinkage

SCA10 Transgenic 500 repeats in 3’ UTR [s25] Motor incoordination
Seizure susceptibility
Loss of CA3 hippocampal neurons

SCA13 Knockout [s26] Motor incoordination No neuronal loss
Zebrafish R420H human mutation [s27] No neuronal loss

SCA14 Transgenic H501Y [s28] Abnormal clasping Altered Purkinje neuron morphology

SCA15/SCA16 Knockout [s29] Motor incoordination Seizures No neuronal loss

SCA17/ Huntington disease like 4 (HDL4) Transgenic 109Q [s30] Motor incoordination Loss of Purkinje neurons

SCA27 Knockout [s31] Cognitive deficits
Motor incoordination
No neuronal loss

DRPLA Transgenic variable repeat length 76Q- 129Q [s32] Cognitive deficits
Motor incoordination
Premature death
Purkinje neuron shrinkage and progressive brain atrophy
a

Refers to mouse models unless otherwise specified.

s1

Burright, E.N., et al., SCA1 transgenic mice: a model for neurodegeneration caused by an expanded CAG trinucleotide repeat. Cell, 1995. 82(6): p. 937–48.

s2

Watase, K., et al., 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(6): p. 905–19.

s3

Xia, H., et al., RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat Med, 2004. 10(8): p. 816–20.

s4

Watase, K., et al., Lithium therapy improves neurological function and hippocampal dendritic arborization in a spinocerebellar ataxia type 1 mouse model. PLoS Med, 2007. 4(5): p. e182.

s5

Cvetanovic, M., et al., Vascular endothelial growth factor ameliorates the ataxic phenotype in a mouse model of spinocerebellar ataxia type 1. Nat Med, 2011. 17(11): p. 1445–7.

s6

Hansen, S.T., et al., Changes in Purkinje cell firing and gene expression precede behavioral pathology in a mouse model of SCA2. Hum Mol Genet, 2012.

s7

Liu, J., et al., Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 2. J Neurosci, 2009. 29(29): p. 9148–62.

s8

Kasumu, A.W., et al., Selective positive modulator of calcium-activated potassium channels exerts beneficial effects in a mouse model of spinocerebellar ataxia type 2. Chem Biol, 2012. 19(10): p. 1340–53.

s9

Chou, A.H., et al., Polyglutamine-expanded ataxin-3 causes cerebellar dysfunction of SCA3 transgenic mice by inducing transcriptional dysregulation. Neurobiol Dis, 2008. 31(1): p. 89–101.

s10

Boy, J., et al., A transgenic mouse model of spinocerebellar ataxia type 3 resembling late disease onset and gender-specific instability of CAG repeats. Neurobiol Dis, 2010. 37(2): p. 284–93.

s11

Goti, D., et al., 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(45): p. 10266–79.

s12

Silva-Fernandes, A., et al., 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(1): p. 163–76.

s13

Boy, J., et al., Reversibility of symptoms in a conditional mouse model of spinocerebellar ataxia type 3.Hum Mol Genet, 2009. 18(22): p. 4282–95.

s14

Cemal, C.K., et al., YAC transgenic mice carrying pathological alleles of the MJD1 locus exhibit a mild and slowly progressive cerebellar deficit. Hum Mol Genet, 2002. 11(9): p. 1075–94.

s15

Chen, X., et al., Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 3. J Neurosci, 2008. 28(48): p. 12713–24.

s16

Shakkottai, V.G., et al., Early changes in cerebellar physiology accompany motor dysfunction in the polyglutamine disease spinocerebellar ataxia type 3. J Neurosci, 2011. 31(36): p. 13002–14.

s17

Alves, S., et al., Striatal and nigral pathology in a lentiviral rat model of Machado-Joseph disease. Hum Mol Genet, 2008. 17(14): p. 2071–83.

s18

. Warrick, J.M., et al., Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in Drosophila. Cell, 1998. 93(6): p. 939–49.

s19

Chou, A.H., et al., HDAC inhibitor sodium butyrate reverses transcriptional downregulation and ameliorates ataxic symptoms in a transgenic mouse model of SCA3. Neurobiol Dis, 2011. 41(2): p. 481–8.

s20

Alves, S., et al., Silencing ataxin-3 mitigates degeneration in a rat model of Machado-Joseph disease: no role for wild-type ataxin-3? Hum Mol Genet, 2010. 19(12): p. 2380–94.

s21

Perkins, E.M., et al., 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(14): p. 4857–67.

s22

Watase, K., et al., 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(33): p. 11987–92.

s23

Furrer, S.A., et al., Spinocerebellar ataxia type 7 cerebellar disease requires the coordinated action of mutant ataxin-7 in neurons and glia, and displays non-cell-autonomous bergmann glia degeneration. J Neurosci, 2011. 31(45): p. 16269–78.

s24

He, Y., et al., 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(39): p. 9975–82.

s25

White, M., et al., Transgenic mice with SCA10 pentanucleotide repeats show motor phenotype and susceptibility to seizure: a toxic RNA gain-of-function model. J Neurosci Res, 2012. 90(3): p. 706–14.

s26

Hurlock, E.C., A. McMahon, and R.H. Joho, Purkinje-cell-restricted restoration of Kv3.3 function restores complex spikes and rescues motor coordination in Kcnc3 mutants. J Neurosci, 2008. 28(18): p. 4640–8.

s27

Issa, F.A., et al., Spinocerebellar ataxia type 13 mutant potassium channel alters neuronal excitability and causes locomotor deficits in zebrafish. J Neurosci, 2011. 31(18): p. 6831–41.

s28

Zhang, Y., et al., Loss of Purkinje cells in the PKCgamma H101Y transgenic mouse. Biochem Biophys Res Commun, 2009. 378(3): p. 524–8.

s29

Matsumoto, M., et al., Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-trisphosphate receptor. Nature, 1996. 379(6561): p. 168–71.

s30

Chang, Y.C., et al., Neuroprotective effects of granulocyte-colony stimulating factor in a novel transgenic mouse model of SCA17. J Neurochem, 2011. 118(2): p. 288–303.

s31

Wang, Q., et al., Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14.Neuron, 2002. 35(1): p. 25–38.

s32

Sato, T., et al., Severe neurological phenotypes of Q129 DRPLA transgenic mice serendipitously created by en masse expansion of CAG repeats in Q76 DRPLA mice. Hum Mol Genet, 2009. 18(4): p. 723–36.

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