{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:23:30Z","timestamp":1790832210566,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR061900"],"award-info":[{"award-number":["AR061900"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder caused by mutations in the DMD gene and the subsequent lack of dystrophin protein. Recently, phosphorodiamidate morpholino oligomer (PMO)-antisense oligonucleotides (ASOs) targeting exon 51 or 53 to reestablish the DMD reading frame have received regulatory approval as commercially available drugs. However, their applicability and efficacy remain limited to particular patients. Large animal models and exon skipping evaluation are essential to facilitate ASO development together with a deeper understanding of dystrophinopathies. Using recombinant adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer, we generated a Yucatan miniature pig model of DMD with an exon 52 deletion mutation equivalent to one of the most common mutations seen in patients. Exon 52-deleted mRNA expression and dystrophin deficiency were confirmed in the skeletal and cardiac muscles of DMD pigs. Accordingly, dystrophin-associated proteins failed to be recruited to the sarcolemma. The DMD pigs manifested early disease onset with severe bodywide skeletal muscle degeneration and with poor growth accompanied by a physical abnormality, but with no obvious cardiac phenotype. We also demonstrated that in primary DMD pig skeletal muscle cells, the genetically engineered exon-52 deleted pig DMD gene enables the evaluation of exon 51 or 53 skipping with PMO and its advanced technology, peptide-conjugated PMO. The results show that the DMD pigs developed here can be an appropriate large animal model for evaluating in vivo exon skipping efficacy.<\/jats:p>","DOI":"10.3390\/ijms222313065","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T21:19:08Z","timestamp":1638479948000},"page":"13065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A Dystrophin Exon-52 Deleted Miniature Pig Model of Duchenne Muscular Dystrophy and Evaluation of Exon Skipping"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1573-4819","authenticated-orcid":false,"given":"Yusuke","family":"Echigoya","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada"},{"name":"Laboratory of Biomedical Science, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kanagawa 252-0880, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhu","family":"Trieu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada"},{"name":"Microscopy & Microanalysis Facility, University of New Brunswick, Fredericton, NB E3A 5A3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2239-9094","authenticated-orcid":false,"given":"William","family":"Duddy","sequence":"additional","affiliation":[{"name":"Northern Ireland Centre for Stratified Medicine, Altnagelvin Hospital Campus, Ulster University, Londonderry BT47 6SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong M.","family":"Moulton","sequence":"additional","affiliation":[{"name":"Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HaiFang","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, School of Medical Technology, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence A.","family":"Partridge","sequence":"additional","affiliation":[{"name":"Research Center for Genetic Medicine, Children\u2019s National Medical Center, Department of Integrative Systems Biology, George Washington University School of Medicine, Washington, DC 20010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Binghamton University, State University of New York, Binghamton, NY 13902, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe N.","family":"Kornegay","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank A.","family":"Rohret","sequence":"additional","affiliation":[{"name":"Precigen Exemplar, 2656 Crosspark Rd. STE 100, Coralville, IA 52241, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Precigen Exemplar, 2656 Crosspark Rd. STE 100, Coralville, IA 52241, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/0092-8674(87)90579-4","article-title":"Dystrophin: The protein product of the Duchenne muscular dystrophy locus","volume":"51","author":"Hoffman","year":"1987","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.nmd.2014.03.008","article-title":"A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy","volume":"24","author":"Mah","year":"2014","journal-title":"Neuromuscul. 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