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. Overall design: Transcriptomic analysis (RNASeq) was performed on samples from striatum, cortex and cerebellum collected from wild type and heterozygous Q130KI rats at 10, 19, and 24 months; at 10 and 19 months, the number of replicates is 5 males/5 females for age/genotype/tissue combinations and at 24 months, the number of replicates is 2-4 males/2-3 females. Twelve samples from GSE152443 (striatum samples from 2 and 6 months animals, male only, 3 animals for each timepoint/genotype) were added as pipeline controls to monitor for reproducibility and batch effect.