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 CAG triplet repeat in Machado-Joseph disease. Here we report the indu ction of apoptosis in cultured cells expressing a portion of the MJD1 gene that includes the expanded CAG repeats. Cell death occurs only wh en the CAG repeat is translated into polyglutamine residues, which app arently precipitate in large covalently modified forms. We also create d ataxic transgenic mice by expressing the expanded polyglutamine stre tch in Purkinje cells. Our results demonstrate the potential involveme nt of the expanded polyglutamine as the common aetiological agent for inherited neurodegenerative diseases with CAG expansions.