{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T10:33:49Z","timestamp":1793010829251,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"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","id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006207","name":"Fusion Energy Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006207","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":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X\u2010linked dystrophinopathies caused by mutations in the dystrophin (\n DMD<\/jats:italic>\n ) gene. A common DMD\u2010causing mutation in humans is exon 52 deletion (\n DMD<\/jats:italic>\n \u039452), which disrupts the reading frame and abolishes dystrophin expression. Therapeutic skipping of exon 51 or 53 can restore the reading frame, producing a truncated but functional protein and generating a BMD\u2010like phenotype. Porcine models recapitulating\n DMD<\/jats:italic>\n \u039452 (DMD) and\n DMD<\/jats:italic>\n \u039451\u201352 (BMD\u2010like) were used to identify molecular differences and condition\u2010specific miRNA\u2013mRNA networks.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Skeletal muscle (triceps brachii) from four DMD, four BMD, and five wild\u2010type (WT) pigs at 3.5\u2009months of age underwent stranded total RNA\u2010seq and small RNA\u2010seq. Differentially expressed mRNAs (|log2FC|\u2009\u2265\u20091, adj.\n p<\/jats:italic>\n \u2009\u2264\u20090.05) and miRNAs (adj.\n p<\/jats:italic>\n \u2009\u2264\u20090.05) were identified with DESeq2. miRNA\u2013mRNA networks were constructed using RNAhybrid predictions (MFE\u2009<\u2009\u221225\u2009kcal\/mol, seed pairing) filtered by inverse Pearson correlation.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Compared with WT, DMD muscle exhibited 1440 upregulated and 487 downregulated genes, characterized by strong repression of structural, contractile, calcium\u2010handling and metabolic genes (e.g.,\n MYBPC2<\/jats:italic>\n ,\n MYL3<\/jats:italic>\n ,\n MYLK2<\/jats:italic>\n ,\n CACNA2D3<\/jats:italic>\n ,\n CACNA2D4<\/jats:italic>\n ) and marked upregulation of inflammatory mediators and innate immune receptors (e.g.,\n IL6<\/jats:italic>\n ,\n IL18<\/jats:italic>\n ,\n IL1R1<\/jats:italic>\n ,\n CCR1\/2\/5<\/jats:italic>\n ,\n TLR1\/2\/4\/7\/9<\/jats:italic>\n ). In contrast, BMD muscle showed partial restoration of these pathways and clustered closer to WT in global expression profiles. Distinct miRNA signatures were observed between DMD and BMD. Differential expression analysis identified 22 upregulated and 12 downregulated miRNAs in DMD versus WT and 36 upregulated and 21 downregulated miRNAs in BMD versus WT. Integration of miRNA and mRNA data yielded extensive regulatory networks (1013 unique pairs for upregulated miRNAs in DMD; 2679 pairs for downregulated miRNAs in BMD). Two condition\u2010specific miRNAs emerged as strong biomarker candidates: ssc\u2010miR\u2010296\u20103p (upregulated exclusively in DMD, targeting 228 genes enriched in muscle structure and fatty acid metabolism) and ssc\u2010miR\u2010423\u20105p (elevated specifically in BMD, targeting 67 genes involved in calcium signalling and tissue development). Several dysregulated miRNAs, including miR\u2010199a\u20105p and miR\u2010199b, overlapped with those reported in human DMD and other muscular dystrophies.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Exon 51 skipping in the\n DMD<\/jats:italic>\n \u039452 background partially restores key transcriptional programmes in skeletal muscle but does not fully normalize them to WT patterns. The identification of condition\u2010specific miRNAs highlights post\u2010transcriptional regulatory differences between DMD and BMD, positioning them as promising biomarkers and therapeutic targets. These findings underscore the translational value of porcine dystrophinopathy models for mechanistic studies and preclinical evaluation of RNA\u2010targeted interventions.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70337","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:57:36Z","timestamp":1788850656000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MicroRNA\u2013mRNA Networks in Skeletal Muscle of Tailored Pig Models for Dystrophinopathies"],"prefix":"10.1002","volume":"17","author":[{"given":"Sarah","family":"Reschke","sequence":"first","affiliation":[{"name":"Chair of Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences LMU Munich Munich Germany"},{"name":"Laboratory for Functional Genome Analysis (LAFUGA), Gene Center LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Graf","sequence":"additional","affiliation":[{"name":"Chair of Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences LMU Munich Munich Germany"},{"name":"Laboratory for Functional Genome Analysis (LAFUGA), Gene Center LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frieder","family":"Hadlich","sequence":"additional","affiliation":[{"name":"Working Group Physiological Genomics Research Institute for Farm Animal Biology (FBN) Dummerstorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Jaudas","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 Oberschlei\u00dfheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Fr\u00f6hlich","sequence":"additional","affiliation":[{"name":"Laboratory for Functional Genome Analysis (LAFUGA), Gene Center LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Stirm","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 Oberschlei\u00dfheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai","family":"Klymiuk","sequence":"additional","affiliation":[{"name":"Center for Innovative Medical Models (CiMM) LMU Munich Oberschlei\u00dfheim Germany"},{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin I TUM Klinikum rechts der Isar Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Krebs","sequence":"additional","affiliation":[{"name":"Chair of Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences LMU Munich Munich Germany"},{"name":"Laboratory for Functional Genome Analysis (LAFUGA), Gene Center LMU Munich Munich 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 of Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences LMU Munich Munich Germany"},{"name":"Laboratory for Functional Genome Analysis (LAFUGA), Gene Center LMU Munich Munich Germany"},{"name":"Center for Innovative Medical Models (CiMM) LMU Munich Oberschlei\u00dfheim Germany"},{"name":"Interfaculty Center for Endocrine and Cardiovascular Disease Network Modelling and Clinical Transfer (ICONLMU) LMU Munich Munich Germany"},{"name":"German Center for Child and Adolescent Diseases (DZKJ) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asghar","family":"Ali","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 Oberschlei\u00dfheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101885"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90579-4"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103387"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2024.04.013"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2022.190"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84863-w"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20586"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00248-3"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abd5758"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt287"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.049285"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2301250120"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.70084"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw237"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep28097"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2022.2058817"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708115104"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25116108"},{"key":"e_1_2_8_20_1","unstructured":"M.Stirm \u201cGeneration and Characterization of a Porcine Model for Becker Muscular Dystrophy\u201d (doctoral dissertation lmu 2023)."},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0294236"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adk9145"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.20517\/jtgg.2025.57"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2301250120"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2021.11.004"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2022.03.003"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-023-08763-0"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.62"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2018.07.003"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2018.12.052"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12266"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2023.05.023"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20181002"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25901"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-020-00444-1"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-01952-2"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12296"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/os.13232"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.012263"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2021.11.037"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes15050606"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.003198"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.219006"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.135576"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0118229"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090479"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv460"},{"issue":"8","key":"e_1_2_8_48_1","first-page":"542","article-title":"Myotonic ADR\u2010MDX Mutant Mice Show Less Severe Muscular Dystrophy Than MDX Mice","volume":"8","author":"Kr\u00e4mer R.","year":"1998","journal-title":"Neuromuscular Disorders"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-017-0124-z"},{"issue":"3","key":"e_1_2_8_50_1","first-page":"351","article-title":"Changes in Muscle Metabolism Are Associated With Phenotypic Variability in Golden Retriever Muscular Dystrophy","volume":"90","author":"Nghiem P. P.","year":"2017","journal-title":"Yale Journal of Biology and Medicine"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep33362"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-14756-9"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-017-0257-2"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70337","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.70337","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70337","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T09:49:52Z","timestamp":1793008192000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.70337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":52,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/jcsm.70337"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.70337","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]},"assertion":[{"value":"2025-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70337"}}