Androgen receptor mutation in Kennedy's disease

Kennedy's disease is an X-linked form of motor neuron disease caused by an expanded polyglutamine repeat in the androgen receptor. While the expansion mutation causes some loss of transcriptional activity by the androgen rece ptor, the predominant effect of expansion is probably a toxic gain of funct ion, similar to the mechanism of other polyglutamine expansion diseases. Fe atures of the neurodegenerative phenotype of Kennedy's disease have now bee n reproduced in transgenic animals and neuronal cell culture. Nuclear inclu sions of mutant androgen receptor protein are found in these model systems and in autopsy samples from patients with Kennedy's disease.