Early onset deficits on the delayed alternation task in the HdhQ92 knock-in mouse model of Huntington's disease

A number of genetic mouse models of Huntington's disease have been created, in order to examine the pathogenesis of Huntington's disease and to test potential therapeutics. In the present study we demonstrate that the full-length knock-in homozygote HdhQ92 mice exhibit impairments at 5 months of age on the delayed alternation task, conducted in 9-hole operant chambers. This test is sensitive to cortico-striatal dysfunction and demonstrates again that although HdhQ92 mice do not display an overt motor phenotype, they do exhibit clear impairments that can be related to deficits seen in HD patients. This indicates that if appropriately sensitive tasks are used, the more subtle and specific HdhQ92 knock-in model could be of use for the examination of pathogenic mechanisms in Huntington's disease and to test potential therapeutics.

► The delayed alternation task is sensitive to fronto-striatal dysfunction. ► 12 month old HdhQ92 mice have previously been tested and were severely impaired. ► In this study HdhQ92 mice were tested on the task. ► At 5 months and 12 months of age the HdhQ92 mice were impaired, but less severely than the previous cohort.