Characterisation of progressive motor deficits in whisker movements in R6/2, Q175 and Hdh knock-in mouse models of Huntington's disease

Background: Motor dysfunction is a major component of the Huntington's disease (HD) phenotype, both in patients and animal models. Motor function in mice is usually measured using tests that involve a novel environment, or require a degree of learning, which creates potential confounds in animals, such as anxiety and/or learning. New method: We propose that studying whisker control provides a more naturalistic way to measure motor function in HD mice. To this end we tested three strains of HD mice; R6/2 (CAG250), zQ175 and Hdh (CAG50, 150 and 250) mice. Results: We discovered a clear and progressive whisking deficit in the most severe model, the R6/2 CAG250 mouse. At 10 weeks, R6/2 mice showed an increase in whisking movements, which may be a correlate of the hyperkinesia seen in HD patients. By 18 weeks the R6/2 mice showed a reduction in whisking movements. Hdh Q250 mice showed a hyperkinetic profile at 10 weeks, approximately 4 months before other motor deficits have previously been reported in these mice. Q175 mice showed very little change in whisking behaviour, apart from a transient increase in retraction velocity at 10 weeks. Comparisons with existing methods: Our findings suggest that whisking may be a more sensitive test of motor function in HD mice than more commonly used methods, such as the rotarod. Conclusions: Our data suggest that whisking deficits represent a novel way of assessing the progression of the motor phenotype, and are early indicators for reversal of phenotype studies, such as drug trials. (C) 2017 Elsevier B.V. All rights reserved.