Transcriptome profiling in knock-in mouse models of Huntington's disease [Liver_miRNA]

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). Knock-in mouse models of HD with human exon 1 containing expanded CAG repeats inserted in the murine huntingtin gene (Hdh) provide a genetic reconstruction of the human causative mutation within the mouse model. The goal of this study is RNA expression profiling by RNA sequencing (RNA-seq) in 2, 6, and 10 month old knock-in mice with CAG lengths of 20, 80, 92, 111, 140, 175 along with littermate control wild-type animals miRNA expression profiles were obtained via RNA-seq analysis performed on tissue samples from the liver of 2, 6, and 10 month old knock-in mice with CAG lengths of 20, 80, 92, 111, 140, 175 along with littermate control wild-type animals.亨廷顿舞蹈病（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、认知及精神异常为主要特征。该疾病的致病突变位于编码亨廷顿蛋白（huntingtin, Htt）的基因编码区，表现为异常扩增且不稳定的CAG三核苷酸重复序列。将携带有扩增CAG重复序列的人类外显子1插入小鼠亨廷顿基因（Hdh）所构建的HD基因敲入小鼠模型，可在小鼠体内重现人类致病突变的遗传背景。本研究的目标为：对CAG重复长度分别为20、80、92、111、140、175的2、6、10月龄基因敲入小鼠及其同窝野生型对照动物，通过RNA测序（RNA sequencing, RNA-seq）开展RNA表达谱分析；同时通过对上述同基因型2、6、10月龄基因敲入小鼠及同窝野生型对照的肝脏组织样本进行RNA-seq分析，获取其miRNA表达谱。