Behavioral Characterization of B6.HttQ175/+ Huntington’s Disease Model Mice

Huntington’s disease (HD) is a fatal autosomal dominant neurodegenerative disease caused by a polyglutamine-coding (CAGs) repeat expansion in the Huntingtin (HTT) gene. The length of polyglutamine repeats are inversely correlated with age of disease onset. HD is defined by a triad of symptoms including cognitive impairment, movement disorders, and mood changes. HD is characterized by the loss of predominantly medium-sized spiny neurons (MSNs) in the striatum which can lead to motor dysfunctions in HD patients. Cognitive and psychiatric changes can appear 10-15 years prior to the onset of motor symptoms of HD. An important advancement in our understanding of HD derives from knock-in HD mouse models that capture the characteristics of human HD. Our previous research has been focused on characterizing behavioral phenotypes in B6.HttQ111/+ mice which have 111 glutamine repeats and display anxiety and apathetic phenotypes beginning around 9 months of age. Here, we began early characterization of the progression of these same phenotypes in B6.HttQ175/+ HD mice, which harbor 175 glutamine repeats in the mutant allele. We used an open field task to measure exploratory behavior as a proxy for anxiety and a balance beam to measure subtle motor deficits in the same mice at 3- and 6-months of age. We will discuss the phenotypic progression and the implications for using the B6.HttQ175/+ mouse model for preclinical HD research