DEVELOPMENT OF CELLULAR AND ANIMAL MODELS FOR HUNTINGTONS DISEASE

点击翻译按钮获取中文摘要

HD is an autosomal dominant, progressive, neurodegenerative disorder with onset generally in midlife. Clinical manifestations of HD include chorea, dementia and other neuropsychiatric disturbances with onset generally in mid-life though juvenile forms of the disease exist. The identification of the HD gene in an international collaboration including this PI in 1993, showed a polymorphic tandem (CAG)n trinucleotide repeat in exon 1 where the normal repeat size range is from 11 to 34 copies. When the repeats exceed 40, HD is the consequence. The repeats are encoded into polyglutamines in the 348 kD huntingtin protein. We have generated full length normal and mutated cDNA constructs for expression in neuronal cell lines in order to elucidate the "gain of function" effect of the poly-Q expanded protein. We have also made a series of mouse HD transgenic lines with varying repeat sizes (16, 48 and 89 CAGs) and are studying them for behavioral phenotype and neuropathology.