Automated motor function phenotyping in mice via home cage voluntary wheel running: Cross-lab validation and comparison with rotarod

At present, the most commonly used method for assessing motor function in rodents is the rotarod. To complement rotarod studies, as part of a collaborative European project (www.phenoscale.com), our aim was to automate and validate the use of home cage based running wheels, including a complex wheel lacking bars, to measure motor function in mice (TSE Systems). In baseline studies at two test centres (CNR and MRC), differences in coping mechanisms to optimize complex wheel running were detectable in inbred mouse strains including C67BL/6NTac, C57BL/6J, 129P2/OlaHsd and C3H/HeH. To further validate the test, we studied wheel running performance in a number of mouse mutant lines expected to show motor function deficits. We investigated motor function in two genetic models of progressive neurodegenerative disease, Huntington's Disease, TgN(HD82Gln)81Dbo (HD) and Amyotrophic Lateral Sclerosis, Tg(SOD1G93A)dl1/GurJ (SOD1), and in a mutant strain with subtle gait abnormalities C-Snap25Bdr/H (Blind drunk, Bdr). In addition, performance on rotarod and grip strength tests was measured at different ages. Several parameters of motor behaviour were considered and analysed through Principal Component Analysis (PCA) in order to detect what motor indices may be comparable between tests and may be more representative for the assessment of motor function in each inbred line or mutant strain. It was observed that, while rotarod performance is similar between mutant and wild-type HD mice at 12 weeks of age, only mutants show an impairment of motor activity on running wheels. Similarly, while no effect of mutation is detected in the rotarod, some parameters of running activity suggest running difficulties in SOD1 mutants at 23 weeks, making this tool a potential method to detect motor deficits at pre-symptomatic stages in mouse models of neurodegenerative disease.