A broad phenotypic screen identifies novel dominant phenotypes in Huntington’s disease CAG knock-in mice

Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder characterized by abnormal voluntary and involuntary movements, cognitive impairment and psychiatric disturbances. In order to identify phenotypic changes in the mouse that are most likely to be relevant to events triggered by the CAG repeat expansion in HD patients, we are interested in the earliest events that are triggered by expression of a single allele’s worth of full-length mutant huntingtin in the mouse, whether at the molecular, cellular or whole animal level. To this end, we have undertaken a broad-based, unbiased phenotypic screen in heterozygous HdhQ111/+ C57BL/6J mice. For expression profiling analysis, four male mice at the age of 18 weeks were analysed versus a pool of four male wildtype mice (reference) at the same age. For each single mouse, two chip hybridizations, including a dye-swap experiment, were performed per tissue. Using our genome-wide microarray platform, we performed transcriptome analysis of liver and brain.