{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:27:04Z","timestamp":1785414424425,"version":"3.56.0"},"posted":{"date-parts":[[2025,9,16]]},"group-title":"Physiology","reference-count":37,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["P50-AR052646"],"award-info":[{"award-number":["P50-AR052646"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01hhm9k47","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Duchenne muscular dystrophy (DMD) is a lethal pediatric degenerative muscle disease for which there is no cure. Robust preclinical models that recapitulate major clinical features of DMD are required to investigate efficacy of potential DMD therapeutics. Rat models of DMD have emerged as promising small animal models to accomplish this; however, there have been no comprehensive studies investigating the functional skeletal muscle decrements associated with the modeling of DMD in rats.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    CRISPR\/Cas9 gene editing was used to generate a dystrophin-deficient Sprague-Dawley muscular dystrophy rat (MDR). Biochemical and immunofluorescent analyses were performed to confirm loss of dystrophin in striated muscles of this rat model.\n                    <jats:italic>In situ<\/jats:italic>\n                    and\n                    <jats:italic>ex vivo<\/jats:italic>\n                    muscle function was assessed in wild-type (WT) and MDR muscles at 3, 6, and 12 months of age, followed by histopathological analyses.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>MDR muscle tissues exhibited loss of full-length dystrophin and reduced content of other dystrophin glycoprotein complex members. MDR extensor digitorum longus (EDL) muscles and diaphragms displayed pronounced and progressive muscle weakness beginning at 3 months of age, compared to WT littermates. EDLs also exhibit susceptibility to eccentric contraction-induced damage. Functional deficits in soleus muscles were less severe and were associated with a right shift in force-frequency relationship and a muscle fiber-type shift. MDR muscles display progressive histopathology including degenerative lesions, fibrosis, regenerative foci, and modest adipose deposition.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>MDR is a preclinical model of DMD that exhibits many translational features of the human disease, including a large dynamic range of muscle decrements, that has high utility for the evaluation of potential therapeutics for DMD.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.09.11.675592","type":"posted-content","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T01:25:14Z","timestamp":1758072314000},"source":"Crossref","is-referenced-by-count":0,"title":["Functional and structural pathologies in skeletal muscle of a rat model of Duchenne muscular dystrophy"],"prefix":"10.64898","author":[{"given":"Young il","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cora C.","family":"Hart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Spencer Henley-Beasley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Herr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Zerpa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7401-4398","authenticated-orcid":false,"given":"Elisabeth R.","family":"Barton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2129-4047","authenticated-orcid":false,"given":"David W.","family":"Hammers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Lee Sweeney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025091904050856000_2025.09.11.675592v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90579-4"},{"key":"2025091904050856000_2025.09.11.675592v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2014.03.008"},{"key":"2025091904050856000_2025.09.11.675592v1.3","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-017-0631-3"},{"key":"2025091904050856000_2025.09.11.675592v1.4","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23528"},{"key":"2025091904050856000_2025.09.11.675592v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00248-3"},{"key":"2025091904050856000_2025.09.11.675592v1.6","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1183101"},{"key":"2025091904050856000_2025.09.11.675592v1.7","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S93873"},{"key":"2025091904050856000_2025.09.11.675592v1.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.4.1189"},{"key":"2025091904050856000_2025.09.11.675592v1.9","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.018424"},{"issue":"2","key":"2025091904050856000_2025.09.11.675592v1.10","doi-asserted-by":"crossref","first-page":"C409","DOI":"10.1152\/ajpcell.00212.2021","article-title":"Murine models of Duchenne muscular dystrophy: is there a best model?","volume":"321","year":"2021","journal-title":"Am J Physiol Cell Physiol"},{"key":"2025091904050856000_2025.09.11.675592v1.11","doi-asserted-by":"crossref","unstructured":"van Putten M , Lloyd EM , de Greef JC , Raz V , Willmann R , Grounds MD : Mouse models for muscular dystrophies: an overview. 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