{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:29:28Z","timestamp":1791397768313,"version":"4.3.3"},"reference-count":60,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,1,12]]},"abstract":"<jats:p>The LMNA gene encodes lamins A and C, two intermediate filament-type proteins that are important determinants of interphase nuclear architecture. Mutations in LMNA lead to a wide spectrum of human diseases including autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD), which affects skeletal and cardiac muscle. The cellular mechanisms by which mutations in LMNA cause disease have been elusive. Here, we demonstrate that defects in neuromuscular junctions (NMJs) are part of the disease mechanism in AD-EDMD. Two AD-EDMD mouse models show innervation defects including misexpression of electrical activity\u2013dependent genes and altered epigenetic chromatin modifications. Synaptic nuclei are not properly recruited to the NMJ because of mislocalization of nuclear envelope components. AD-EDMD patients with LMNA mutations show the same cellular defects as the AD-EDMD mouse models. These results suggest that lamin A\/C\u2013mediated NMJ defects contribute to the AD-EDMD disease phenotype and provide insights into the cellular and molecular mechanisms for the muscle-specific phenotype of AD-EDMD.<\/jats:p>","DOI":"10.1083\/jcb.200811035","type":"journal-article","created":{"date-parts":[[2009,1,5]],"date-time":"2009-01-05T20:44:50Z","timestamp":1231188290000},"page":"31-44","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":111,"title":["Lamin A\/C\u2013mediated neuromuscular junction defects in Emery-Dreifuss muscular dystrophy"],"prefix":"10.1083","volume":"184","author":[{"given":"Alexandre","family":"Me\u0301jat","sequence":"first","affiliation":[{"name":"1National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vale\u0301rie","family":"Decostre","sequence":"additional","affiliation":[{"name":"2Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unite Mixte de Recherche U582, Institut de Myologie, Paris F-75013, France"},{"name":"3Universite\u0301 Pierre et Marie Curie, University Paris 06, Unite Mixte de Recherche S582, Institut Federatif de Recherche 14, Paris F-75013, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Li","sequence":"additional","affiliation":[{"name":"4School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Renou","sequence":"additional","affiliation":[{"name":"2Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unite Mixte de Recherche U582, Institut de Myologie, Paris F-75013, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akanchha","family":"Kesari","sequence":"additional","affiliation":[{"name":"5Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Hantai\u0308","sequence":"additional","affiliation":[{"name":"2Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unite Mixte de Recherche U582, Institut de Myologie, Paris F-75013, France"},{"name":"3Universite\u0301 Pierre et Marie Curie, University Paris 06, Unite Mixte de Recherche S582, Institut Federatif de Recherche 14, Paris F-75013, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin L.","family":"Stewart","sequence":"additional","affiliation":[{"name":"6Institute of Medical Biology, Immunos, Singapore City 138668, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Xiao","sequence":"additional","affiliation":[{"name":"4School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Hoffman","sequence":"additional","affiliation":[{"name":"5Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gise\u0300le","family":"Bonne","sequence":"additional","affiliation":[{"name":"2Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unite Mixte de Recherche U582, Institut de Myologie, Paris F-75013, France"},{"name":"3Universite\u0301 Pierre et Marie Curie, University Paris 06, Unite Mixte de Recherche S582, Institut Federatif de Recherche 14, Paris F-75013, France"},{"name":"7Assistance Publique, Ho\u0302pitaux de Paris, Groupe Hospitalier Pitie\u0301 Salpe\u0302trie\u0300re, Unite\u0301 Fonctionnelle de Cardioge\u0301ne\u0301tique et Myoge\u0301ne\u0301tique, Service de Biochimie Me\u0301tabolique, Paris F-75013, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Misteli","sequence":"additional","affiliation":[{"name":"1National Cancer Institute, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2009,1,5]]},"reference":[{"key":"2023072300074088900_BIB1","doi-asserted-by":"crossref","first-page":"31986","DOI":"10.1074\/jbc.M004775200","volume":"275","year":"2000","journal-title":"J. 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