{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:38:56Z","timestamp":1791092336210,"version":"4.1.0"},"reference-count":27,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":2694,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>Deficits in motor function are debilitating features in disorders affecting neurological, neuromuscular and musculoskeletal systems. Although these can vary greatly with respect to age of onset, symptomatic presentation, rate of progression and severity, the study of these disease models in mice is confined to use of a small number of tests, most commonly the Rotarod test. To expand the repertoire of meaningful motor function tests in mice, we tested, optimised and validated an automated home-cage based running-wheel system, incorporating a conventional wheel with evenly-spaced rungs and a complex wheel with particular rungs absent. The system enables automated assessment of motor function without handler interference which is desirable in longitudinal studies involving continuous monitoring of motor performance. In baseline studies at two test centres, consistently significant differences in performance on both wheels were detectable among four common inbred strains. As further validation, we studied performance in mutant 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 both models of progressive disease, as with the third mutant, we could reliably and consistently detect specific motor function deficits at ages far earlier than any previously-recorded symptoms in vivo, 7-8 weeks for the HD mice and 12 weeks for the SOD1 mice. This included longitudinal analysis of Rotarod and grip strength performance where deficits were still not detectable at 12 weeks and 23 weeks respectively. Several new parameters of motor behaviour were uncovered using Principal Component Analysis, indicating that the wheel-running assay could record features of motor function that are independent of Rotarod performance. This represents a powerful new method to detect motor deficits at pre-symptomatic stages in mouse disease models and should be considered as a valid tool to investigate the efficacy of therapeutic agents.<\/jats:p>","DOI":"10.1242\/dmm.013946","type":"journal-article","created":{"date-parts":[[2014,1,15]],"date-time":"2014-01-15T01:26:42Z","timestamp":1389749202000},"source":"Crossref","is-referenced-by-count":26,"title":["Early motor deficits in mouse disease models are reliably uncovered using an automated home cage wheel-running system: a cross-laboratory validation"],"prefix":"10.1242","author":[{"given":"Silvia","family":"Mandillo","sequence":"first","affiliation":[{"name":"CNR - Inst. Cell Biol. and Neurobiology-EMMA, Monterotondo Scalo, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Heise","sequence":"additional","affiliation":[{"name":"MRC Harwell, Oxfordshire, UK;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Garbugino","sequence":"additional","affiliation":[{"name":"CNR - Inst. Cell Biol. and Neurobiology-EMMA, Monterotondo Scalo, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glauco P.","family":"Tocchini-Valentini","sequence":"additional","affiliation":[{"name":"CNR - Inst. Cell Biol. and Neurobiology-EMMA, Monterotondo Scalo, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Istituto Superiore di Sanita, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Wells","sequence":"additional","affiliation":[{"name":"MRC Harwell, Oxfordshire, UK;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick M.","family":"Nolan","sequence":"additional","affiliation":[{"name":"MRC Harwell, Oxfordshire, UK;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2014,1,1]]},"reference":[{"key":"2021042501164836100_b1-0070397","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1242\/dmm.007237","article-title":"A comprehensive assessment of the SOD1G93A low-copy transgenic mouse, which models human amyotrophic lateral sclerosis","volume":"4","author":"Acevedo-Arozena","year":"2011","journal-title":"Dis. 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