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 [s14–16] |
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 |
Refers to mouse models unless otherwise specified.
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