{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:08:00Z","timestamp":1790842080583,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1009179","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000}}],"reference-count":107,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:00:00Z","timestamp":1605052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR40864-27"],"award-info":[{"award-number":["AR40864-27"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["AR065139-02"],"award-info":[{"award-number":["AR065139-02"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR44533-22"],"award-info":[{"award-number":["AR44533-22"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["Developmental Grant"],"award-info":[{"award-number":["Developmental Grant"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Gene therapy approaches for DMD using recombinant adeno-associated viral (rAAV) vectors to deliver miniaturized (or micro) dystrophin genes to striated muscles have shown significant progress. However, concerns remain about the potential for immune responses against dystrophin in some patients. Utrophin, a developmental paralogue of dystrophin, may provide a viable treatment option. Here we examine the functional capacity of an rAAV-mediated microutrophin (\u03bcUtrn) therapy in the<jats:italic>mdx<\/jats:italic><jats:sup><jats:italic>4cv<\/jats:italic><\/jats:sup>mouse model of DMD. We found that rAAV-\u03bcUtrn led to improvement in dystrophic histopathology &amp; mostly restored the architecture of the neuromuscular and myotendinous junctions. Physiological studies of tibialis anterior muscles indicated peak force maintenance, with partial improvement of specific force. A fundamental question for \u03bcUtrn therapeutics is not only can it replace critical functions of dystrophin, but whether full-length utrophin impacts the therapeutic efficacy of the smaller, highly expressed \u03bcUtrn. As such, we found that \u03bcUtrn significantly reduced the spacing of the costameric lattice relative to full-length utrophin. Further, immunostaining suggested the improvement in dystrophic pathophysiology was largely influenced by favored correction of fast 2b fibers. However, unlike \u03bcUtrn, \u03bcdystrophin (\u03bcDys) expression did not show this fiber type preference. Interestingly, \u03bcUtrn was better able to protect 2a and 2d fibers in<jats:italic>mdx<\/jats:italic>:utrn<jats:sup>-\/-<\/jats:sup>mice than in<jats:italic>mdx<\/jats:italic><jats:sup><jats:italic>4cv<\/jats:italic><\/jats:sup>mice where the endogenous full-length utrophin was most prevalent. Altogether, these data are consistent with the role of steric hindrance between full-length utrophin &amp; \u03bcUtrn within the sarcolemma. Understanding the stoichiometry of this effect may be important for predicting clinical efficacy.<\/jats:p>","DOI":"10.1371\/journal.pgen.1009179","type":"journal-article","created":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T18:44:17Z","timestamp":1605120257000},"page":"e1009179","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Microutrophin expression in dystrophic mice displays myofiber type differences in therapeutic effects"],"prefix":"10.1371","volume":"16","author":[{"given":"Glen B.","family":"Banks","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5299-0059","authenticated-orcid":true,"given":"Jeffrey 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individuals","volume":"50","author":"M Koenig","year":"1987","journal-title":"Cell"},{"issue":"4","key":"pgen.1009179.ref003","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.jmb.2005.07.064","article-title":"Molecular extensibility of mini-dystrophins and a dystrophin rod construct","volume":"352","author":"N Bhasin","year":"2005","journal-title":"Journal of molecular biology"},{"issue":"9","key":"pgen.1009179.ref004","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1016\/j.bbapap.2010.03.009","article-title":"A biophysical map of the dystrophin rod","volume":"1804","author":"A Mirza","year":"2010","journal-title":"Biochimica et biophysica acta"},{"issue":"21","key":"pgen.1009179.ref005","doi-asserted-by":"crossref","first-page":"9632","DOI":"10.1073\/pnas.1001517107","article-title":"Disease-causing missense mutations in actin binding domain 1 of dystrophin induce thermodynamic instability and protein aggregation","volume":"107","author":"DM Henderson","year":"2010","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"pgen.1009179.ref006","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0074-7696(07)65005-0","article-title":"Biology of the striated muscle dystrophin-glycoprotein complex","volume":"265","author":"JM Ervasti","year":"2008","journal-title":"Int Rev Cytol"},{"issue":"6","key":"pgen.1009179.ref007","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/0092-8674(91)90035-W","article-title":"Membrane organization of the dystrophin-glycoprotein complex","volume":"66","author":"JM Ervasti","year":"1991","journal-title":"Cell"},{"issue":"8","key":"pgen.1009179.ref008","doi-asserted-by":"crossref","first-page":"4560","DOI":"10.1016\/S0021-9258(19)39599-7","article-title":"Detailed analysis of the repeat domain of dystrophin reveals four potential hinge segments that may confer flexibility","volume":"265","author":"M Koenig","year":"1990","journal-title":"The Journal of biological chemistry"},{"issue":"6273","key":"pgen.1009179.ref009","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/345315a0","article-title":"Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle","volume":"345","author":"JM Ervasti","year":"1990","journal-title":"Nature"},{"issue":"2","key":"pgen.1009179.ref010","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":"JM Ervasti","year":"2007","journal-title":"Biochim Biophys Acta"},{"issue":"7221","key":"pgen.1009179.ref011","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nature07414","article-title":"Sarcolemma-localized nNOS is required to maintain activity after mild exercise","volume":"456","author":"YM Kobayashi","year":"2008","journal-title":"Nature"},{"issue":"4","key":"pgen.1009179.ref012","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/12034","article-title":"Role for alpha-dystrobrevin in the pathogenesis of dystrophin-dependent muscular dystrophies","volume":"1","author":"RM Grady","year":"1999","journal-title":"Nat Cell Biol"},{"issue":"2","key":"pgen.1009179.ref013","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1023\/A:1005364713451","article-title":"Rapid recovery following contraction-induced injury to in situ skeletal muscles in mdx mice","volume":"19","author":"SV Brooks","year":"1998","journal-title":"Journal of muscle research and cell motility"},{"issue":"5","key":"pgen.1009179.ref014","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1023\/A:1014587918367","article-title":"Tibialis anterior muscles in mdx mice are highly susceptible to contraction-induced injury","volume":"22","author":"C Dellorusso","year":"2001","journal-title":"Journal of muscle research and cell motility"},{"issue":"7","key":"pgen.1009179.ref015","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1111\/j.1440-1681.2007.04865.x","article-title":"Diaphragm muscle strip preparation for evaluation of gene therapies in mdx mice","volume":"35","author":"JA Faulkner","year":"2008","journal-title":"Clinical and experimental pharmacology & physiology"},{"issue":"4","key":"pgen.1009179.ref016","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1007\/BF00121296","article-title":"Increased susceptibility of EDL muscles from mdx mice to damage induced by contractions with stretch","volume":"14","author":"P Moens","year":"1993","journal-title":"J Muscle Res Cell Motil"},{"issue":"8","key":"pgen.1009179.ref017","doi-asserted-by":"crossref","first-page":"3710","DOI":"10.1073\/pnas.90.8.3710","article-title":"Dystrophin protects the sarcolemma from stresses developed during muscle contraction","volume":"90","author":"BJ Petrof","year":"1993","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"12","key":"pgen.1009179.ref018","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/BF01187915","article-title":"Structure and function of the neuromuscular junction in young adult mdx mice","volume":"20","author":"PR Lyons","year":"1991","journal-title":"Journal of neurocytology"},{"issue":"4","key":"pgen.1009179.ref019","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.mcn.2008.12.011","article-title":"Truncated dystrophins can influence neuromuscular synapse structure","volume":"40","author":"GB Banks","year":"2009","journal-title":"Mol Cell Neurosci"},{"issue":"10","key":"pgen.1009179.ref020","article-title":"Myofiber branching rather than myofiber hyperplasia contributes to muscle hypertrophy in mdx mice","volume":"4","author":"RM Faber","year":"2014","journal-title":"Skeletal 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neurology"},{"issue":"2","key":"pgen.1009179.ref024","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/mus.880180211","article-title":"Site and mechanics of failure in normal and dystrophin-deficient skeletal muscle","volume":"18","author":"DJ Law","year":"1995","journal-title":"Muscle & nerve"},{"issue":"5","key":"pgen.1009179.ref025","first-page":"1513","article-title":"Dystrophin deficiency is associated with myotendinous junction defects in prenecrotic and fully regenerated skeletal muscle","volume":"142","author":"DJ Law","year":"1993","journal-title":"The American journal of pathology"},{"issue":"24","key":"pgen.1009179.ref026","doi-asserted-by":"crossref","first-page":"3975","DOI":"10.1093\/hmg\/ddn301","article-title":"Molecular and cellular adaptations to chronic myotendinous strain injury in mdx mice expressing a truncated dystrophin","volume":"17","author":"GB Banks","year":"2008","journal-title":"Human molecular 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Biol"},{"issue":"3","key":"pgen.1009179.ref030","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.jmb.2009.04.025","article-title":"Mapping of the lipid-binding and stability properties of the central rod domain of human dystrophin","volume":"389","author":"S Legardinier","year":"2009","journal-title":"Journal of molecular biology"},{"issue":"43","key":"pgen.1009179.ref031","doi-asserted-by":"crossref","first-page":"28419","DOI":"10.1074\/jbc.273.43.28419","article-title":"A cluster of basic repeats in the dystrophin rod domain binds F-actin through an electrostatic interaction","volume":"273","author":"KJ Amann","year":"1998","journal-title":"The Journal of biological chemistry"},{"issue":"3","key":"pgen.1009179.ref032","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1172\/JCI36612","article-title":"Dystrophins carrying spectrin-like repeats 16 and 17 anchor nNOS to the sarcolemma and enhance exercise performance in a mouse model of muscular dystrophy","volume":"119","author":"Y Lai","year":"2009","journal-title":"J Clin Invest"},{"issue":"17","key":"pgen.1009179.ref033","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.1093\/hmg\/ddy197","article-title":"Syntrophin binds directly to multiple spectrin-like repeats in dystrophin and mediates binding of nNOS to repeats 16\u201317","volume":"27","author":"ME Adams","year":"2018","journal-title":"Hum Mol Genet"},{"issue":"15","key":"pgen.1009179.ref034","doi-asserted-by":"crossref","first-page":"5723","DOI":"10.1073\/pnas.1323842111","article-title":"Microtubule binding distinguishes dystrophin from utrophin","volume":"111","author":"JJ Belanto","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"pgen.1009179.ref035","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1177\/0883073810371006","article-title":"Preclinical studies for gene therapy of Duchenne muscular dystrophy","volume":"25","author":"GL Odom","year":"2010","journal-title":"J Child Neurol"},{"issue":"R1","key":"pgen.1009179.ref036","doi-asserted-by":"crossref","first-page":"R69","DOI":"10.1093\/hmg\/ddr105","article-title":"Therapeutic approaches to muscular dystrophy","volume":"20","author":"A Goyenvalle","year":"2011","journal-title":"Human molecular genetics"},{"issue":"7","key":"pgen.1009179.ref037","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/nm1439","article-title":"rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice","volume":"12","author":"P Gregorevic","year":"2006","journal-title":"Nat Med"},{"issue":"4","key":"pgen.1009179.ref038","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/jor.20781","article-title":"Systemic human minidystrophin gene transfer improves functions and life span of dystrophin and dystrophin\/utrophin-deficient mice","volume":"27","author":"B Wang","year":"2009","journal-title":"Journal of orthopaedic research: 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Shin","year":"2013","journal-title":"Mol Ther"},{"issue":"R1","key":"pgen.1009179.ref042","doi-asserted-by":"crossref","first-page":"R102","DOI":"10.1093\/hmg\/ddz128","article-title":"AAV-based gene therapies for the muscular dystrophies","volume":"28","author":"JM Crudele","year":"2019","journal-title":"Hum Mol Genet"},{"issue":"9","key":"pgen.1009179.ref043","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1089\/hum.2013.092","article-title":"Anti-dystrophin T cell responses in Duchenne muscular dystrophy: prevalence and a glucocorticoid treatment effect","volume":"24","author":"KM Flanigan","year":"2013","journal-title":"Hum Gene Ther"},{"issue":"6","key":"pgen.1009179.ref044","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nrg3460","article-title":"Therapy for Duchenne muscular dystrophy: renewed optimism from genetic approaches","volume":"14","author":"RJ Fairclough","year":"2013","journal-title":"Nature reviews 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Tinsley","year":"1998","journal-title":"Nat Med"},{"issue":"14","key":"pgen.1009179.ref054","doi-asserted-by":"crossref","first-page":"9161","DOI":"10.1016\/S0021-9258(18)31565-5","article-title":"Purification of dystrophin from skeletal muscle","volume":"266","author":"JM Ervasti","year":"1991","journal-title":"The Journal of biological chemistry"},{"issue":"1","key":"pgen.1009179.ref055","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1083\/jcb.112.1.135","article-title":"Dystrophin-glycoprotein complex is highly enriched in isolated skeletal muscle sarcolemma","volume":"112","author":"K Ohlendieck","year":"1991","journal-title":"The Journal of cell biology"},{"issue":"5","key":"pgen.1009179.ref056","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1093\/oxfordjournals.jbchem.a123276","article-title":"Glycoprotein complex anchoring dystrophin to sarcolemma","volume":"108","author":"M Yoshida","year":"1990","journal-title":"Journal of 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