SCA7 mice recapitulate CNS- PNS and retina pathologies and show a transcriptional signature of Purkinje cell dysfunction prevailing in SCA1 and SCA2 mice


Institut de Genetique et de Biologie Moleculaire et Cellulaire

Molecular Neurodegeneration

Here we describe the first SCA7 knock-in mice that combine most cardinal features of SCA7, including retinal, cerebellar, cerebral and peripheral nerves pathologies, which account for progressive impairment of behavior, motor and vision functions. MRI and brain morphometry reveal atrophy of grey and white matter of specific cerebral regions, while peripheral nerves and photoreceptors show functional and morphological alterations. We show that cerebellar pathology is characterized by gene deregulation in all cerebellar cell types and alterations of SAGA-dependent epigenetic marks. Intranuclear accumulation of mutant ATXN7 and gene downregulation precede the onset of PC pacemaker dysfunction. Interestingly, PC show loss of expression of 83 PC-specific genes coding for ion channels, receptors and signaling proteins involved in pacemaker function and long-term depression, which are causal factors of many type of ataxias. Comparison of cerebellar transcriptome with other SCAs reveals a subset of 67 PC-specific genes downregulated in SCA1, SCA2 and SCA7, providing a common signature of early PC dysfunction.

BIOSEB Instruments Used:
Aron Test or Four Plates Test (LE830),Grip strength test (BIO-GS3),Rotarod (BX-ROD)

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