Transcriptional profiling of brain tissues from a Q130 Long Evans Knock-in rat model of Huntington’s disease at 10-, 19- and 24-months of age

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that is characterized by motor, cognitive, and psychiatric alterations. The mutation responsible for this disease is an abnormally expanded and unstable CAG repeat within the coding region of the gene encoding huntingtin (Htt). A collaboration between the CHDI Foundation and Dr. H.P. Nguyen ([e-mail]) at Universitat Bochum focused on generating a knock-in rat model of HD that contains expanded CAG repeats inserted within the rat huntingtin gene (Hdh) in order to provide a genetic reconstruction of the human causative mutation within the rat model. The goal of this study is RNA expression profiling by RNA sequencing (RNA-seq) in brain tissues of 10-, 19- and 24-month-old heterozygous knock-in rats with uninterrupted CAG length approaching 130 along with littermate control wild-type animals.亨廷顿舞蹈症（Huntington's disease, HD）是一种常染色体显性遗传的神经退行性疾病，以运动、认知及精神行为异常为典型特征。该病的致病突变为编码亨廷顿蛋白（huntingtin, Htt）的基因编码区存在异常扩增且不稳定的CAG三核苷酸重复序列。CHDI基金会与波鸿大学的H.P. Nguyen博士（邮箱：[e-mail]）携手开展合作，旨在构建亨廷顿病敲入大鼠模型：该模型在大鼠亨廷顿基因（Hdh）中插入了扩增的CAG重复序列，从而在大鼠模型中实现人类致病突变的遗传重构。本研究的核心目标为：对10月龄、19月龄及24月龄的杂合敲入大鼠（其无间断CAG长度接近130）及其同窝野生型对照动物的脑组织进行RNA测序（RNA sequencing, RNA-seq），以开展基因表达谱分析。