Automated motor function phenotyping in mice via home cage voluntary wheel running:

The study of motor function in mouse models of diseases affecting neurological, neuromuscular and musculoskeletal systems is confined to use of a small number of tests, most commonly the Rotarod. To expand the repertoire of meaningful motor function tests in mice, as part of the EU-funded project PhenoScale, we developed, optimised and validated an automated home-cage based running-wheel system (TSE Systems). Within this system we incorporated a conventional wheel with evenly-spaced rungs and a complex weel with particular rungs absent, as previously described in Liebetanz and Merkler, 2006. We compared baseline test results using four commonly-used inbred strains and three mutant lines, which are models of diseases affecting the motor system, in two test centres (CNR, Monterotondo, Italy and MRC Harwell, UK). We also compared mouse running activity to performance in the Rotarod, and carried out Principal Component Analysis (PCA) including data from both tests. New parameters of motor behaviour were uncovered using PCA, indicating that the wheel-running assay could record features of motor function that are independent of Rotarod performance. Accordingly, motor deficits were observed in mutants' running activity, while their performance in the Rotarod was still unaffected at the same age. Home cage voluntary wheel running assessment may therefore represent a valid and powerful method to detect motor deficits at pre-symptomatic stages.