Repository logo
 

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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Garland, H 
Wood, NI 
Skillings, EA 
Detloff, PJ 
Morton, AJ 

Abstract

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.

Description

Keywords

Rodent behaviour, Active sensing, Motor control, Huntington’s disease, Whisking

Journal Title

Journal of Neuroscience Methods

Conference Name

Journal ISSN

0165-0270
1872-678X

Volume Title

Publisher

Elsevier
Sponsorship
All work was funded via internal grants from the University of Cambridge and Manchester Metropolitan University.