Transcriptional profiling of brain tissues from a Q130 Long Evans Knock-in rat model of Huntington’s disease at 2-, 6- and 12-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 2-, 6- and 12-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性神经退行性疾病，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）的基因编码区中存在异常扩增且不稳定的CAG重复序列。CHDI基金会与波鸿鲁尔大学的H.P. Nguyen博士（邮箱：[e-mail]）合作，旨在构建HD基因敲入大鼠模型：将扩增的CAG重复序列插入大鼠亨廷顿基因（Hdh）内，以实现在大鼠模型中重现人类致病突变的遗传背景。本研究的目标为通过RNA测序（RNA-seq）对2月龄、6月龄及12月龄的杂合子基因敲入大鼠（其连续CAG重复长度接近130）及其同窝野生型对照动物的脑组织开展基因表达谱分析。