{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:04:06Z","timestamp":1790982246499,"version":"4.1.0"},"reference-count":55,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:p>Duchenne muscular dystrophy is characterized by myofiber necrosis, muscle replacement by connective tissue, and crippling weakness. Although the mdx mouse also lacks dystrophin, most muscles show little myofiber loss or functional impairment. An exception is the mdx diaphragm, which is phenotypically similar to the human disease. Here we tested the hypothesis that the mdx diaphragm has a defective regenerative response to necrotic injury, which could account for its severe phenotype. Massive necrosis was induced in mdx and wild-type (C57BL10) mouse diaphragms in vivo by topical application of notexin, which destroys mature myofibers while leaving myogenic precursor satellite cells intact. At 4 h after acute exposure to notexin, &gt;90% of diaphragm myofibers in both wild-type and mdx mice demonstrated pathological sarcolemmal leakiness, and there was a complete loss of isometric force-generating capacity. Both groups of mice showed strong expression of embryonic myosin within the diaphragm at 5 days, which was largely extinguished by 20 days after injury. At 60 days postinjury, wild-type diaphragms exhibited a persistent loss (\u223c25%) of isometric force-generating capacity, associated with a trend toward increased connective tissue infiltration. In contrast, mdx diaphragms achieved complete functional recovery of force generation to noninjured values, and there was no increase in muscle connective tissue over baseline. These data argue against any loss of intrinsic regenerative capacity within the mdx diaphragm, despite characteristic features of major dystrophic pathology being present. Our findings support the concept that significant latent regenerative capacity resides within dystrophic muscles, which could potentially be exploited for therapeutic purposes.<\/jats:p>","DOI":"10.1152\/ajpregu.00146.2004","type":"journal-article","created":{"date-parts":[[2004,6,15]],"date-time":"2004-06-15T18:18:57Z","timestamp":1087323537000},"page":"R961-R968","source":"Crossref","is-referenced-by-count":34,"title":["Regenerative capacity of the dystrophic (mdx) diaphragm after induced injury"],"prefix":"10.1152","volume":"287","author":[{"given":"Stefan","family":"Matecki","sequence":"first","affiliation":[{"name":"Meakins-Christie Laboratories and Respiratory Division, McGill University, Montreal, Quebec, Canada H3A 1A1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghiabe H.","family":"Guibinga","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories and Respiratory Division, McGill University, Montreal, Quebec, Canada H3A 1A1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basil J.","family":"Petrof","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories and Respiratory Division, McGill University, Montreal, Quebec, Canada H3A 1A1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041380213"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880140311"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(199809)21:9<1153::AID-MUS6>3.0.CO;2-6"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200108071"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118101"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.15.4856"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1038\/nature01154"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880080404"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(200005)23:5<784::AID-MUS17>3.0.CO;2-Y"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1994.77.4.1736"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5356.1528"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880150508"},{"key":"R13","doi-asserted-by":"crossref","unstructured":"Guibinga GH, Lochm\u00fcller H, Massie B, Nalbantoglu J, Karpati G, and Petrof BJ.Combinatorial blockade of calcineurin and CD28 signaling facilitates primary and secondary therapeutic gene transfer by adenovirus vectors in dystrophic (mdx) mouse muscles.J Virol72: 4601\u20134609, 1998.","DOI":"10.1128\/JVI.72.6.4601-4609.1998"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2001.0482"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1016\/0892-0354(90)90001-9"},{"key":"R16","doi-asserted-by":"crossref","unstructured":"Heslop L, Morgan JE, and Partridge TA.Evidence for a myogenic stem cell that is exhausted in dystrophic muscle.J Cell Sci113: 2299\u20132308, 2000.","DOI":"10.1242\/jcs.113.12.2299"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63644-9"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90579-4"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1038\/355696a0"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(96)00422-1"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1007\/BF00309633"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1998.9107"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00689.2002"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0453com"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1016\/0960-8966(95)00012-C"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.158.5.9803112"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1016\/0960-8966(95)00006-9"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1016\/0960-8966(93)90098-5"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1007\/BF00212544"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.9.2.493"},{"key":"R31","unstructured":"McNeil PLand Khakee R.Disruptions of muscle fiber plasma membranes. 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