{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:22:33Z","timestamp":1789154553404,"version":"build-2803163510"},"reference-count":60,"publisher":"National Academy of Sciences","issue":"29","license":[{"start":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:00:00Z","timestamp":1688947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002745","name":"Bayerische Forschungsstiftung","doi-asserted-by":"publisher","award":["AZ 802-08 AZ 1536-21"],"award-info":[{"award-number":["AZ 802-08 AZ 1536-21"]}],"id":[{"id":"10.13039\/501100002745","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Else Kr\u00f6ner-Fresenius Stiftung","award":["2015_180"],"award-info":[{"award-number":["2015_180"]}]},{"name":"ForTra gGmbH f\u00fcr Forschungstransfer der EKFS","award":["2018_T20"],"award-info":[{"award-number":["2018_T20"]}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["Grant Agreement No. 812660"],"award-info":[{"award-number":["Grant Agreement No. 812660"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100019180","name":"EC | ERC | HORIZON EUROPE European Research Council","doi-asserted-by":"publisher","award":["101021043"],"award-info":[{"award-number":["101021043"]}],"id":[{"id":"10.13039\/100019180","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,7,18]]},"abstract":"<jats:p>\n                    Duchenne muscular dystrophy (DMD) is a fatal X-linked disease caused by mutations in the\n                    <jats:italic>DMD<\/jats:italic>\n                    gene, leading to complete absence of dystrophin and progressive degeneration of skeletal musculature and myocardium. In DMD patients and in a corresponding pig model with a deletion of\n                    <jats:italic>DMD<\/jats:italic>\n                    exon 52 (\n                    <jats:italic>DMD<\/jats:italic>\n                    \u039452), expression of an internally shortened dystrophin can be achieved by skipping of\n                    <jats:italic>DMD<\/jats:italic>\n                    exon 51 to reframe the transcript. To predict the best possible outcome of this strategy, we generated\n                    <jats:italic>DMD<\/jats:italic>\n                    \u039451-52 pigs, additionally representing a model for Becker muscular dystrophy (BMD).\n                    <jats:italic>DMD<\/jats:italic>\n                    \u039451-52 skeletal muscle and myocardium samples stained positive for dystrophin and did not show the characteristic dystrophic alterations observed in\n                    <jats:italic>DMD<\/jats:italic>\n                    \u039452 pigs. Western blot analysis confirmed the presence of dystrophin in the skeletal muscle and myocardium of\n                    <jats:italic>DMD<\/jats:italic>\n                    \u039451-52 pigs and its absence in\n                    <jats:italic>DMD<\/jats:italic>\n                    \u039452 pigs. The proteome profile of skeletal muscle, which showed a large number of abundance alterations in\n                    <jats:italic>DMD<\/jats:italic>\n                    \u039452 vs. wild-type (WT) samples, was normalized in\n                    <jats:italic>DMD<\/jats:italic>\n                    \u039451-52 samples. Cardiac function at age 3.5 mo was significantly reduced in\n                    <jats:italic>DMD<\/jats:italic>\n                    \u039452 pigs (mean left ventricular ejection fraction 58.8% vs. 70.3% in WT) but completely rescued in\n                    <jats:italic>DMD<\/jats:italic>\n                    \u039451-52 pigs (72.3%), in line with normalization of the myocardial proteome profile. Our findings indicate that ubiquitous deletion of\n                    <jats:italic>DMD<\/jats:italic>\n                    exon 51 in\n                    <jats:italic>DMD<\/jats:italic>\n                    \u039452 pigs largely rescues the rapidly progressing, severe muscular dystrophy and the reduced cardiac function of this model. Long-term follow-up studies of\n                    <jats:italic>DMD<\/jats:italic>\n                    \u039451-52 pigs will show if they develop symptoms of the milder BMD.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2301250120","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T15:06:39Z","timestamp":1689001599000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":18,"title":["Systemic deletion of\n                    <i>DMD<\/i>\n                    exon 51 rescues clinically severe Duchenne muscular dystrophy in a pig model lacking\n                    <i>DMD<\/i>\n                    exon 52"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9729-0670","authenticated-orcid":false,"given":"Michael","family":"Stirm","sequence":"first","affiliation":[{"name":"Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich 81377, Germany"},{"name":"Center for Innovative Medical Models, Department of Veterinary Sciences, LMU Munich, Oberschleissheim 85764, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4558-0785","authenticated-orcid":false,"given":"Bachuki","family":"Shashikadze","sequence":"additional","affiliation":[{"name":"Laboratory for Functional Genome Analysis, Gene Center, LMU Munich, Munich 81377, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Blutke","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Pathology, Center for Clinical Veterinary Medicine, LMU Munich, Munich 80539, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7785-7502","authenticated-orcid":false,"given":"Elisabeth","family":"Kemter","sequence":"additional","affiliation":[{"name":"Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich 81377, Germany"},{"name":"Center for Innovative Medical Models, Department of Veterinary Sciences, LMU Munich, Oberschleissheim 85764, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Lange","sequence":"additional","affiliation":[{"name":"Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich 81377, Germany"},{"name":"Center for Innovative Medical Models, Department of Veterinary Sciences, LMU Munich, Oberschleissheim 85764, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6432-1271","authenticated-orcid":false,"given":"Jan B.","family":"St\u00f6ckl","sequence":"additional","affiliation":[{"name":"Laboratory for Functional Genome Analysis, Gene Center, LMU Munich, Munich 81377, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6684-7712","authenticated-orcid":false,"given":"Florian","family":"Jaudas","sequence":"additional","affiliation":[{"name":"Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich 81377, Germany"},{"name":"Center for Innovative Medical Models, Department of Veterinary Sciences, LMU Munich, Oberschleissheim 85764, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7011-237X","authenticated-orcid":false,"given":"Laeticia","family":"Laane","sequence":"additional","affiliation":[{"name":"Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich 81377, Germany"},{"name":"Center for Innovative Medical Models, Department of Veterinary Sciences, LMU Munich, Oberschleissheim 85764, 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5974-9759","authenticated-orcid":false,"given":"Valeri","family":"Zakhartchenko","sequence":"additional","affiliation":[{"name":"Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich 81377, Germany"},{"name":"Center for Innovative Medical Models, Department of Veterinary Sciences, LMU Munich, Oberschleissheim 85764, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"B\u00e4hr","sequence":"additional","affiliation":[{"name":"Center for Innovative Medical Models, Department of Veterinary Sciences, LMU Munich, Oberschleissheim 85764, Germany"},{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin I, Klinikum rechts der Isar, Technical University Munich, Munich 81675, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai","family":"Klymiuk","sequence":"additional","affiliation":[{"name":"Center for Innovative Medical Models, Department of Veterinary Sciences, LMU Munich, Oberschleissheim 85764, Germany"},{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin I, Klinikum rechts der Isar, Technical University Munich, Munich 81675, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9940-8783","authenticated-orcid":false,"given":"Hiroshi","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Meiji University International Institute for Bio-Resource Research, Kawasaki 214-8571, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7611-4827","authenticated-orcid":false,"given":"Maggie C.","family":"Walter","sequence":"additional","affiliation":[{"name":"Department of Neurology, Friedrich Baur Institute, LMU Munich, Munich 80336, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Wurst","sequence":"additional","affiliation":[{"name":"Institute of Developmental Genetics, Helmholtz Munich, Neuherberg 85674, Germany"},{"name":"Chair of Developmental Genetics, TUM School of Life Sciences, Technische Universit\u00e4t M\u00fcnchen, Freising 85354, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3611-1218","authenticated-orcid":false,"given":"Christian","family":"Kupatt","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin I, Klinikum rechts der Isar, Technical University Munich, Munich 81675, Germany"},{"name":"German Center for Cardiovascular Research, Munich Heart Alliance, Munich 81675, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4709-3211","authenticated-orcid":false,"given":"Thomas","family":"Fr\u00f6hlich","sequence":"additional","affiliation":[{"name":"Laboratory for Functional Genome Analysis, Gene Center, LMU Munich, Munich 81377, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0430-9510","authenticated-orcid":false,"given":"Eckhard","family":"Wolf","sequence":"additional","affiliation":[{"name":"Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich 81377, Germany"},{"name":"Center for Innovative Medical Models, Department of Veterinary Sciences, LMU Munich, Oberschleissheim 85764, Germany"},{"name":"Laboratory for Functional Genome Analysis, Gene Center, LMU Munich, Munich 81377, Germany"},{"name":"Interfaculty Center for Endocrine and Cardiovascular Disease Network Modelling and Clinical Transfer, LMU Munich, Munich 81377, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,7,10]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90579-4"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103387"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00248-3"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20586"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2017.57"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.31662\/jmaj.2021-0019"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S97635"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009233"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.1264"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2004840117"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","unstructured":"C. Kupatt Genome editing for Duchenne muscular dystrophy: A glimpse of the future? Gene. Ther. 28 542\u2013548 (2021).","DOI":"10.1038\/s41434-021-00222-4"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2021.04.002"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad5725"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad5143"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad5177"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008647"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau1549"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt287"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.049285"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0738-2"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv601"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1080\/10409230590918577"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00196"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.151"},{"key":"e_1_3_4_25_2","first-page":"307","article-title":"Embryonic myosin is a regeneration marker to monitor utrophin-based therapies for DMD","volume":"28","author":"Guiraud S.","year":"2019","unstructured":"S. Guiraud , Embryonic myosin is a regeneration marker to monitor utrophin-based therapies for DMD. Hum. Mol. Genet. 28, 307\u2013319 (2019).","journal-title":"Hum. Mol. Genet."},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3233\/JND-160194"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1038"},{"key":"e_1_3_4_28_2","unstructured":"B. Shashikadze T. Fr\u00f6hlich Systemic deletion of DMD exon 51 rescues clinically severe Duchenne muscular dystrophy in a pig model lacking DMD exon 52. PRIDE PRoteomics IDEntifications (PRIDE) Archive. https:\/\/www.ebi.ac.uk\/pride\/archive\/projects\/PXD039533. 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