{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:40:51Z","timestamp":1791960051106,"version":"4.3.4"},"reference-count":72,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2019,8,18]],"date-time":"2019-08-18T00:00:00Z","timestamp":1566086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["573732"],"award-info":[{"award-number":["573732"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Adeno\u2010associated viral vector was used to elevate the expression of muscle specific kinase (MuSK) and rapsyn (a cytoplasmic MuSK effector protein) in the tibialis anterior muscle of wild\u2010type and dystrophic (<jats:italic>mdx<\/jats:italic>) mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In <jats:italic>mdx<\/jats:italic> mice, enhanced expression of either MuSK or rapsyn ameliorated the acute loss of muscle force associated with strain injury.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Increases in sarcolemmal immunolabelling for utrophin and \u03b2\u2010dystroglycan suggest a mechanism for the protective effect of MuSK in <jats:italic>mdx<\/jats:italic> muscles.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>MuSK also caused subtle changes to the structure and function of the neuromuscular junction, suggesting novel roles for MuSK in muscle physiology and pathophysiology.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Muscle specific kinase (MuSK) has a well\u2010defined role in stabilizing the developing mammalian neuromuscular junction, but MuSK might also be protective in some neuromuscular diseases. In the dystrophin\u2010deficient <jats:italic>mdx<\/jats:italic> mouse model of Duchenne muscular dystrophy, limb muscles are especially fragile. We injected the tibialis anterior muscle of 8\u2010week\u2010old <jats:italic>mdx<\/jats:italic> and wild\u2010type (C57BL10) mice with adeno\u2010associated viral vectors encoding either MuSK or rapsyn (a cytoplasmic MuSK effector protein) fused to green fluorescent protein (MuSK\u2010GFP and rapsyn\u2010GFP, respectively). Contralateral muscles injected with empty vector served as controls. One month later mice were anaesthetized with isoflurane and isometric force\u2010producing capacity was recorded from the distal tendon. MuSK\u2010GFP caused an unexpected decay in nerve\u2010evoked tetanic force, both in wild\u2010type and <jats:italic>mdx<\/jats:italic> muscles, without affecting contraction elicited by direct electrical stimulation of the muscle. Muscle fragility was probed by challenging muscles with a strain injury protocol consisting of a series of four strain\u2010producing eccentric contractions <jats:italic>in vivo<\/jats:italic>. When applied to muscles of <jats:italic>mdx<\/jats:italic> mice, eccentric contraction produced an acute 27% reduction in directly evoked muscle force output, affirming the susceptibility of <jats:italic>mdx<\/jats:italic> muscles to strain injury. <jats:italic>mdx<\/jats:italic> muscles overexpressing MuSK\u2010GFP or rapsyn\u2010GFP exhibited significantly milder force deficits after the eccentric contraction challenge (15% and 14%, respectively). The protective effect of MuSK\u2010GFP in muscles of <jats:italic>mdx<\/jats:italic> mice was associated with increased immunolabelling for utrophin and \u03b2\u2010dystroglycan in the sarcolemma. Elevating the expression of MuSK or rapsyn revealed several distinct synaptic and extrasynaptic effects, suggesting novel roles for MuSK signalling in muscle physiology and pathophysiology.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp277839","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T22:43:31Z","timestamp":1564008211000},"page":"4831-4850","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Muscle specific kinase protects dystrophic <i>mdx<\/i> mouse muscles from eccentric contraction\u2010induced loss of force\u2010producing capacity"],"prefix":"10.1113","volume":"597","author":[{"given":"S.","family":"Trajanovska","sequence":"first","affiliation":[{"name":"Physiology and Bosch Institute University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Ban","sequence":"additional","affiliation":[{"name":"Physiology and Bosch Institute University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Huang","sequence":"additional","affiliation":[{"name":"Physiology and Bosch Institute University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Gregorevic","sequence":"additional","affiliation":[{"name":"Department of Physiology The University of Melbourne  Melbourne Victoria Australia"},{"name":"Baker IDI Heart and Diabetes Institute  Melbourne Victoria Australia"},{"name":"Department of Biochemistry and Molecular Biology Monash University  Melbourne Victoria Australia"},{"name":"Department of Neurology University of Washington School of Medicine  Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9484-8050","authenticated-orcid":false,"given":"M.","family":"Morsch","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Macquarie University  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8605-1586","authenticated-orcid":false,"given":"D. 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