DEVELOPMENT OF CELLULAR AND ANIMAL MODELS FOR HUNTINGTONS DISEASE

HD是一种常染色体显性、进行性、神经退行性疾病， 一般在中年发病。HD的临床表现包括舞蹈病， 痴呆和其他神经精神障碍， 中年人虽然青少年形式的疾病存在。识别 HD基因的国际合作，包括本PI， 1993年，在外显子1中发现了多态性串联（CAG）n三核苷酸重复序列 其中正常重复大小范围为11至34个拷贝。当 重复次数超过40次，HD是后果。重复序列被编码成 348 kD亨廷顿蛋白中的多聚谷氨酰胺。我们已经产生了完整的 用于在神经元细胞中表达长度正常和突变的cDNA构建体 为了阐明poly-Q的“功能增益”效应， 膨胀蛋白我们还建立了一系列小鼠HD转基因品系 不同的重复大小（16，48和89 CAG），并正在研究它们， 行为表型和神经病理学。

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.