{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:47:40Z","timestamp":1790524060403,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006662","name":"National Institute on Handicapped Research","doi-asserted-by":"publisher","award":["16NMDB\u2010DB60\u20100004"],"award-info":[{"award-number":["16NMDB\u2010DB60\u20100004"]}],"id":[{"id":"10.13039\/100006662","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006662","name":"National Institute on Handicapped Research","doi-asserted-by":"publisher","award":["CL\u20102018\u201018\u2010008"],"award-info":[{"award-number":["CL\u20102018\u201018\u2010008"]}],"id":[{"id":"10.13039\/100006662","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011724","name":"Muscular Dystrophy UK","doi-asserted-by":"publisher","award":["RA4\/3023\/1"],"award-info":[{"award-number":["RA4\/3023\/1"]}],"id":[{"id":"10.13039\/100011724","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019256","name":"NIHR Great Ormond Street Hospital Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019256","name":"NIHR Great Ormond Street Hospital Biomedical Research Centre","doi-asserted-by":"publisher","award":["759108"],"award-info":[{"award-number":["759108"]}],"id":[{"id":"10.13039\/501100019256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019256","name":"NIHR Great Ormond Street Hospital Biomedical Research Centre","doi-asserted-by":"publisher","award":["MGU0426"],"award-info":[{"award-number":["MGU0426"]}],"id":[{"id":"10.13039\/501100019256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019256","name":"NIHR Great Ormond Street Hospital Biomedical Research Centre","doi-asserted-by":"publisher","award":["MR\/K000608\/1 (Institute of Neurology, University College London)"],"award-info":[{"award-number":["MR\/K000608\/1 (Institute of Neurology, University College London)"]}],"id":[{"id":"10.13039\/501100019256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019256","name":"NIHR Great Ormond Street Hospital Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019256","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":[[2022,4]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Duchenne muscular dystrophy (DMD) is caused by\n DMD<\/jats:italic>\n mutations leading to dystrophin loss. Full\u2010length Dp427 is the primary dystrophin isoform expressed in muscle and is also expressed in the central nervous system (CNS). Two shorter isoforms, Dp140 and Dp71, are highly expressed in the CNS. While a role for Dp140 and Dp71 on DMD CNS comorbidities is well known, relationships between mutations expected to disrupt Dp140 and Dp71 and motor outcomes are not.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Functional outcome data from 387 DMD boys aged 4\u201315\u00a0years were subdivided by\n DMD<\/jats:italic>\n mutation expected effects on dystrophin isoform expression; Group 1 (Dp427 absent, Dp140\/Dp71 present,\n n<\/jats:italic>\n \u00a0=\u00a0201); Group 2 (Dp427\/Dp140 absent, Dp71 present,\n n<\/jats:italic>\n \u00a0=\u00a0152); and Group 3 (Dp427\/Dp140\/Dp71 absent,\n n<\/jats:italic>\n \u00a0=\u00a034). Relationships between isoform group and North Star ambulatory assessment (NSAA) scores, 10\u00a0m walk\/run velocities and rise time velocities were explored using regression analysis.\n <\/jats:p>\n \n Western blot analysis was used to study Dp427, Dp140 and Dp71 production in myogenic cells (control and DMD human), control skeletal muscle, DMD skeletal muscle from the three isoform groups and cerebral cortex from mice (wild\u2010type and DMD models). Grip strength and rotarod running test were studied in wild\u2010type mice and DMD mouse models. DMD mouse models were\n mdx<\/jats:italic>\n (Dp427 absent, Dp140\/Dp71 present),\n mdx52<\/jats:italic>\n (Dp427\/Dp140 absent, Dp71 present) and\n DMD\u2010null<\/jats:italic>\n (lacking all isoforms).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In DMD boys, mean NSAA scores at 5\u00a0years of age were 6.1 points lower in Group 3 than Group 1 (\n P<\/jats:italic>\n \u00a0<\u00a00.01) and 4.9 points lower in Group 3 than Group 2 (\n P<\/jats:italic>\n \u00a0=\u00a00.05). Mean peak NSAA scores were 4.0 points lower in Group 3 than Group 1 (\n P<\/jats:italic>\n \u00a0<\u00a00.01) and 1.6 points lower in Group 2 than Group 1 (\n P<\/jats:italic>\n \u00a0=\u00a00.04).\n <\/jats:p>\n \n Mean four\u2010limb grip strength was 1.5\u00a0g\/g lower in\n mdx52<\/jats:italic>\n than\n mdx<\/jats:italic>\n mice (\n P<\/jats:italic>\n \u00a0=\u00a00.003) and 1.5\u00a0g\/g lower in\n DMD\u2010null<\/jats:italic>\n than\n mdx<\/jats:italic>\n mice (\n P<\/jats:italic>\n \u00a0=\u00a00.002).\n <\/jats:p>\n \n Dp71 was produced in myogenic cells (control and DMD human) and skeletal muscle from humans in Groups 1 and 2 and\n mdx<\/jats:italic>\n mice, but not skeletal muscle from human controls, myogenic cells and skeletal muscle from humans in Group 3 or skeletal muscle from wild\u2010type,\n mdx52<\/jats:italic>\n or\n DMD\u2010null<\/jats:italic>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our results highlight the importance of considering expected effects of\n DMD<\/jats:italic>\n mutations on dystrophin isoform production when considering patterns of DMD motor impairment and the implications for clinical practice and clinical trials. Our results suggest a complex relationship between dystrophin isoforms expressed in the brain and DMD motor function.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.12914","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T23:38:37Z","timestamp":1643240317000},"page":"1360-1372","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Investigating the role of dystrophin isoform deficiency in motor function in Duchenne muscular dystrophy"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6061-2218","authenticated-orcid":false,"given":"Mary","family":"Chesshyre","sequence":"first","affiliation":[{"name":"Dubowitz Neuromuscular Centre UCL Great Ormond Street Institute of Child Health London UK"},{"name":"NIHR Great Ormond Street Hospital Biomedical Research Centre UCL Great Ormond Street Institute of Child Health London 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DMD_M.2.2.001 version 2.0 [Internet]. Treat NMD neuromuscular network.2019[2021 Apr 11].https:\/\/treat\u2010nmd.org\/wp\u2010content\/uploads\/2016\/08\/MDX\u2010DMD_M.2.2.001.pdf"},{"key":"e_1_2_11_36_1","article-title":"Assessing functional performance in the mdx mouse model","volume":"85","author":"Aartsma\u2010Rus A","year":"2014","journal-title":"J Vis Exp"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a124281"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03000"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2018.06.347"},{"key":"e_1_2_11_40_1","unstructured":"Sarepta Therapeutics I. A Randomized Double\u2010blind Placebo\u2010controlled Study of SRP\u20109001 for Duchenne Muscular Dystrophy (DMD) [Internet]. Clinicaltrials.gov [www.clinicaltrials.gov]. 2018 [cited 2021 Oct 5]. 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