{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T16:56:26Z","timestamp":1788886586873,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002745","name":"Bayerische Forschungsstiftung","doi-asserted-by":"publisher","award":["AZ 802\u201008"],"award-info":[{"award-number":["AZ 802\u201008"]}],"id":[{"id":"10.13039\/501100002745","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002745","name":"Bayerische Forschungsstiftung","doi-asserted-by":"publisher","award":["PDOC\u201090\u201015"],"award-info":[{"award-number":["PDOC\u201090\u201015"]}],"id":[{"id":"10.13039\/501100002745","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["23CVD01"],"award-info":[{"award-number":["23CVD01"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["534046536"],"award-info":[{"award-number":["534046536"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Duchenne muscular dystrophy (DMD) is a fatal X\u2010linked disease caused by mutations in the\n DMD<\/jats:italic>\n gene, leading to dystrophin deficiency and progressive degeneration of skeletal and cardiac muscles. Pigs lacking\n DMD<\/jats:italic>\n exon 52 (\n DMD<\/jats:italic>\n \u039452) are a clinically severe model for DMD, mimicking molecular, functional and pathological hallmarks of the human disease. Dystrophin expression can be restored by additionally deleting exon 51 (\n DMD<\/jats:italic>\n \u039451\u201352), which reframes\n DMD<\/jats:italic>\n transcripts and alleviates pathological alterations.\n DMD<\/jats:italic>\n \u039451\u201352 pigs model Becker muscular dystrophy (BMD), a milder and slower\u2010progressing form of muscle degeneration.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The Aurora Swine Isometric Footplate Test Apparatus was used to quantify functional parameters of the hind limb dorsiflexor muscle group of 3.5\u2010month\u2010old DMD pigs (\n n<\/jats:italic>\n \u2009=\u20095), BMD pigs (\n n<\/jats:italic>\n \u2009=\u20093) and wild\u2010type (WT) littermate controls (\n n<\/jats:italic>\n \u2009=\u20093). In addition, histopathological and proteomic studies of the functionally tested muscles were performed.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n After twitch stimulation, DMD muscle achieved 62.4% (\n p<\/jats:italic>\n \u2009<\u20090.05) and BMD muscle 67.1% (\n p<\/jats:italic>\n \u2009<\u20090.05) of the absolute peak force of WT muscle, indicating partial but not complete restoration of muscle force by\n DMD<\/jats:italic>\n \u039451\u201352 transcript reframing. After normalization to the cube root of body mass, the values were 70.9% for DMD muscle (\n p<\/jats:italic>\n \u2009=\u20090.05) and 65.8% for BMD muscle (\n p<\/jats:italic>\n \u2009<\u20090.05). DMD muscle showed a reduced rate of contraction (\n p<\/jats:italic>\n \u2009<\u20090.01); the rate of relaxation was decreased in both DMD (\n p<\/jats:italic>\n \u2009<\u20090.01) and BMD (\n p<\/jats:italic>\n \u2009<\u20090.05) compared with WT muscle. After tetanic stimulation, DMD muscle reached 54.7% (\n p<\/jats:italic>\n \u2009<\u20090.001) and BMD muscle 80.4% (\n p<\/jats:italic>\n \u2009=\u20090.08) of WT muscle force. Normalized values were 62.7% (DMD;\n p<\/jats:italic>\n \u2009<\u20090.01) and 79.3% (BMD;\n p<\/jats:italic>\n \u2009=\u20090.08). The rate of contraction was reduced in both DMD (\n p<\/jats:italic>\n \u2009<\u20090.001) and BMD muscle (\n p<\/jats:italic>\n \u2009<\u20090.01), whereas the return to the resting state was prolonged (\n p<\/jats:italic>\n \u2009<\u20090.001) only in DMD vs. WT muscle. Histopathology and proteomics revealed no significant differences between BMD and WT muscles, whereas severe alterations were observed in DMD pigs.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our study pioneers the quantitative assessment of skeletal muscle function in dystrophic pigs. It demonstrates that systemic exon 51 skipping in DMD caused by loss of\n DMD<\/jats:italic>\n exon 52 partially restores muscle function but does not achieve WT levels. These findings highlight the value of dynamic muscle force measurements as a sensitive tool to evaluate the efficacy of therapeutic interventions in the porcine DMD model.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70084","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T08:49:10Z","timestamp":1759308550000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Reduced Muscle Force in Dystrophic\n DMD<\/i>\n \u039452 Pigs Is Incompletely Restored by Systemic Transcript Reframing (\n DMD<\/i>\n \u039451\u201352)"],"prefix":"10.1002","volume":"16","author":[{"given":"Michaela","family":"Blasi","sequence":"first","affiliation":[{"name":"Chair of Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences LMU Munich Munich Germany"},{"name":"Center for Innovative Medical Models (CiMM) LMU Munich Munich 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Diseases (DZKJ) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Kessler","sequence":"additional","affiliation":[{"name":"Chair of Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences LMU Munich Munich Germany"},{"name":"Center for Innovative Medical Models (CiMM) LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep\u00a0M.","family":"Cambra","sequence":"additional","affiliation":[{"name":"Center for Innovative Medical Models (CiMM) LMU Munich Munich Germany"},{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin I TUM Klinikum Rechts der Isar Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeri","family":"Zakhartchenko","sequence":"additional","affiliation":[{"name":"Chair of Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences LMU Munich Munich Germany"},{"name":"Center for Innovative Medical Models (CiMM) LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie\u00a0C.","family":"Walter","sequence":"additional","affiliation":[{"name":"Friedrich Baur Institute at the Department of Neurology LMU University Hospital, LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kupatt","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin I TUM Klinikum Rechts der Isar Munich Germany"},{"name":"German Center for Cardiovascular Research (DZHK) Munich Heart Alliance Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai","family":"Klymiuk","sequence":"additional","affiliation":[{"name":"Center for Innovative Medical Models (CiMM) LMU Munich Munich Germany"},{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin I TUM Klinikum Rechts der Isar Munich 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