Assessing Nucleocytoplasmic transport in Spinocerebellar Ataxia type 7

AbstractSCA7 is an autosomal dominant CAG/polyglutamine trinucleotide repeat expansion disease that accounts for ~4% of all spinocerebellar ataxias in the USA. In addition to atrophy of the cerebellar cortex and brainstem, an important feature of SCA7, that allows it to be distinguished from the 40+ other SCAs, is a cone-rod dystrophy form of retinal degeneration. Recent studies of ALS and CAG-polyglutamine trinucleotide repeat expansion neurodegenerative diseases indicate that nuclear membrane dysfunction and impaired nucleocytoplasmic transport could play pivotal roles in SCA7 disease pathogenesis; hence, here we will examine the nuclear membrane and nucleocytoplasmic transport in the retina and cerebellum of SCA7 mice and in neuronal models of SCA7 disease to determine if alteration of these cellular processes is contributing to SCA7 retinal and cerebellar degeneration.