{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:50:47Z","timestamp":1784955047507,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PS 169193, FDN 143251, PJ51772"],"award-info":[{"award-number":["PS 169193, FDN 143251, PJ51772"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alberta Innovates Health Solutions","award":["FS G2019000283"],"award-info":[{"award-number":["FS G2019000283"]}]},{"DOI":"10.13039\/100010090","name":"Women and Children\u2019s Health Research Institute","doi-asserted-by":"publisher","award":["IG 2115"],"award-info":[{"award-number":["IG 2115"]}],"id":[{"id":"10.13039\/100010090","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Heart &amp; Stroke Foundation","award":["561422"],"award-info":[{"award-number":["561422"]}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","award":["950-232166"],"award-info":[{"award-number":["950-232166"]}],"id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","award":["RES0045114"],"award-info":[{"award-number":["RES0045114"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dystrophin is a 427 kDa protein that stabilizes muscle cell membranes through interactions with the cytoskeleton and various membrane-associated proteins. Loss of dystrophin as in Duchenne muscular dystrophy (DMD) causes progressive skeletal muscle weakness and cardiac dysfunction. Multiple promoters along the dystrophin gene (DMD) give rise to a number of shorter isoforms. Of interest is Dp71, a 71 kDa isoform implicated in DMD pathology by various animal and patient studies. Strong evidence supporting such a role for Dp71, however, is lacking. Here, we use del52;WT mice to understand how Dp71 overexpression affects skeletal and cardiac muscle phenotypes. Apart from the mouse Dmd gene, del52;WT mice are heterozygous for a full-length, exon 52-deleted human DMD transgene expected to only permit Dp71 expression in muscle. Thus, del52;WT mice overexpress Dp71 through both the human and murine dystrophin genes. We observed elevated Dp71 protein in del52;WT mice, significantly higher than wild-type in the heart but not the tibialis anterior. Moreover, del52;WT mice had generally normal skeletal muscle but impaired cardiac function, exhibiting significant systolic dysfunction as early as 3 months. No histological abnormalities were found in the tibialis anterior and heart. Our results suggest that Dp71 overexpression may have more detrimental effects on the heart than on skeletal muscles, providing insight into the role of Dp71 in DMD pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms222312617","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T04:48:37Z","timestamp":1638247717000},"page":"12617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Natural History of a Mouse Model Overexpressing the Dp71 Dystrophin Isoform"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5484-4183","authenticated-orcid":false,"given":"Kenji Rowel Q.","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Nur Ahad","family":"Shah","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1661-3499","authenticated-orcid":false,"given":"Stanley","family":"Woo","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"}]},{"given":"Harry","family":"Wilton-Clark","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0652-3235","authenticated-orcid":false,"given":"Pavel","family":"Zhabyeyev","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2G3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2G3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5656-6930","authenticated-orcid":false,"given":"Rika","family":"Maruyama","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9154-9028","authenticated-orcid":false,"given":"Gavin Y.","family":"Oudit","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2G3, Canada"},{"name":"Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2B7, Canada"}],"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"},{"name":"Muscular Dystrophy Canada Research Chair, Edmonton, AB T6G 2H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.bbadis.2006.05.010","article-title":"Dystrophin, its interactions with other proteins, and implications for muscular dystrophy","volume":"1772","author":"Ervasti","year":"2007","journal-title":"Biochim. 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