Differential susceptibility of cultured cell lines to aggregate formation and cell death produced by the truncated Machado-Joseph disease gene product with an expanded polyglutamine stretch.

Ataxin-3, a protein coded by the Machado-Joseph disease gene, possesses a polyglutamine stretch whose expansion is known to produce neuronal intranuclear inclusion and neurodegeneration. Although previous studies describe the aggregate formation and toxic effect of the expanded polyglutamine tract in vitro and in vivo, differences in the susceptibility of different cultured cell lines has not been reported. Using the plasmid expressing N-terminal truncated ataxin-3 with an expanded polyglutamine stretch, we evaluated the aggregate formation and cytotoxicity in eight cultured cell lines-HeLa, Swiss/3T3, P19, C2C12, COS-1, BHK-21, PC12, and Neuro2a-that demonstrated a diverse range of aggregate formation and cell death. Although aggregate frequency did not appear to be correlated with cell death, Neuro2a demonstrated a high frequency of both. Our data indicates that susceptibility to cell death produced by mutant truncated ataxin-3 differs significantly among different cell lines and provides useful information when using a cultured cell line as an in vitro cellular model of polyglutamine disease.