Transcriptional changes in mouse models in SCA3

The study examined early transcriptional changes in the brain of different mouse models of spinocerebellar ataxia type 3, a dominantly-inherited neurodegenerative disease caused by a CAG repeat expansion in the ATXN3 gene. The goal was to identify early transcriptional signatures that are strongly associated with the accumulation and aggregation of the disease protein, ataxin-3, in the brain. The study also investigated the extent to which the observed transcriptional changes might be contributors to disease pathogenesis. Overall design: The overall study includes multiple different RNA-seq runs utilizing wild-type, two different knock-in mouse models of SCA3 (a traditional and variant), two different transgenic models of SCA3 (Q84 and Q15), and an ataxin-3 knock-out mouse. In total, 19 wild-type mice, 13 homozygous variant knock-in mice, 6 heterozygous variant knock-in mice, 4 traditional homozygous knock-in mice, 4 traditional heterozygous knock-in mice, 4 Q84 transgenic mice, 4 Q15 transgenic mice, and 3 ataxin-3 knock-out mice. The majority of the study examined the pons of the mice, and with one smaller run examining the deep cerebellar nuclei of wild-type and variant homozygous knock-in mice (n=3 each).

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Ramani B, Panwar B, Moore LR, Wang B, Huang R, Guan Y, Paulson HL