Mitochondria-associated apoptosis in the pathogenesis of SCA3

Machado-Joseph disease (MJD) or Spinocerebellar Ataxia Type 3 (SCA3) is the most common type of SCA worldwide. SCA3 is an autosomal dominant neurodegenerative disorder caused by polyglutamine-expanded ataxin-3, whose function is still unknown. To better understand the function of Ataxin-3 in vivo, we analysed Ataxin-3 mutant mice generated by the gene trap (GT) approach. The genetrap model harboured a truncated ataxin-3 including the Josephin domain and the first ubiquitin inactive motif (UIM1), but lacking the VCP binding site and the polyQ stretch. By expressing only the Josephin domain and UIM1 we got a SCA3…