EXON-1 OF THE HD GENE WITH AN EXPANDED CAG REPEAT IS SUFFICIENT TO CAUSE A PROGRESSIVE NEUROLOGICAL PHENOTYPE IN TRANSGENIC MICE

Huntington's disease (HD) is one of an increasing number of neurodegen erative disorders caused by a CAG/ polyglutamine repeat expansion. Mic e have been generated that are transgenic for the 5' end of the human HD gene carrying (CAG)(115)-(CAG)(150) repeat expansions. In three lin es, the transgene is ubiquitously expressed at both mRNA and protein l evel. Transgenic mice exhibit a progressive neurological phenotype tha t exhibits many of the features of HD, including choreiform-like movem ents, involuntary stereotypic movements, tremor, and epileptic seizure s, as well as nonmovement disorder components. This transgenic model w ill greatly assist in an eventual understanding of the molecular patho logy of HD and may open the way to the testing of intervention strateg ies.