Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo

Recently, we identified a novel gene, MJD1 , which contains an expanded GAG triplet repeat in Machado–Joseph disease. Here we report the induction of apoptosis in cultured cells expressing a portion of the MJD1 gene that includes the expanded GAG repeats. Cell death occurs only when the GAG repeat is translated into polyglutamine residues, which apparently precipitate in large covalently modified forms. We also created ataxic transgenic mice by expressing the expanded polyglutamine stretch in Purkinje cells. Our results demonstrate the potential involvement of the expanded polyglutamine as the common aetiological agent for inherited neurodegenerative diseases with GAG expansions.