{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:10:45Z","timestamp":1790665845428,"version":"4.1.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2019,10,19]],"date-time":"2019-10-19T00:00:00Z","timestamp":1571443200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centre national de la recherche scientifique"},{"DOI":"10.13039\/501100003768","name":"University of Strasbourg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003768","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-IDEX-0002-02"],"award-info":[{"award-number":["ANR-10-IDEX-0002-02"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-LABX-0030-INRT"],"award-info":[{"award-number":["ANR-10-LABX-0030-INRT"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007393","name":"Association Fran\u00e7aise contre les Myopathies","doi-asserted-by":"publisher","award":["21267-RESCUE"],"award-info":[{"award-number":["21267-RESCUE"]}],"id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Dynamin 2 (DNM2) is a ubiquitously expressed GTPase implicated in many cellular functions such as membrane trafficking and cytoskeleton regulation. Dominant mutations in DNM2 result in tissue specific diseases affecting peripheral nerves (Charcot-Marie-Tooth neuropathy, CMT) or skeletal muscles (Centronuclear myopathy, CNM). However, the reason for this tissue specificity is unknown, and it remains unclear if these diseases share a common pathomechanism. To compare the disease pathophysiological mechanisms in skeletal muscle, we exogenously expressed wild-type DNM2 (WT-DNM2), the DNM2-CMT mutation K562E, or DNM2-CNM mutations R465W and S619L causing adult and neonatal forms respectively, by intramuscular adeno-associated virus (AAV) injections. All muscles expressing exogenous WT-DNM2 and CNM or CMT mutations exhibited reduced muscle force. However, only expression of CNM mutations and WT-DNM2 correlated with CNM-like histopathological hallmarks of nuclei centralization and reduced fiber size. The extent of alterations correlated with clinical severity in patients. Ultrastructural and immunofluorescence analyses highlighted defects of the triads, mitochondria and costameres as major causes of the CNM phenotype. Despite the reduction in force upon expression of the DNM2-CMT mutation, muscle histology and ultrastructure were almost normal. However, the neuromuscular junction was affected in all DNM2 injected muscles, with the DNM2-CMT mutation inducing the most severe alterations, potentially explaining the reduction in force observed with this mutant. In conclusion, expression of WT and CNM mutants recreate a CNM-like phenotype, suggesting CNM mutations are gain-of-function. Histological, ultrastructural and molecular analyses pointed to key pathways uncovering the different pathomechanisms involved in centronuclear myopathy or Charcot-Marie-Tooth neuropathy linked to DNM2 mutations.<\/jats:p>","DOI":"10.1093\/hmg\/ddz249","type":"journal-article","created":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T15:40:54Z","timestamp":1570722054000},"source":"Crossref","is-referenced-by-count":12,"title":["Different in vivo impact of Dynamin 2 mutations implicated in Charcot-Marie-Tooth neuropathy or Centronuclear Myopathy"],"prefix":"10.1093","author":[{"given":"X\u00e8nia Massana","family":"Mu\u00f1oz","sequence":"first","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Illkirch, France"},{"name":"Centre National de la Recherche Scientifique, UMR7104, Illkirch, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1258, Illkirch, France"},{"name":"Universit\u00e9 de Strasbourg, Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzie","family":"Buono","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Illkirch, France"},{"name":"Centre National de la Recherche Scientifique, UMR7104, Illkirch, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1258, Illkirch, France"},{"name":"Universit\u00e9 de Strasbourg, Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Koebel","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Illkirch, France"},{"name":"Centre National de la Recherche Scientifique, UMR7104, Illkirch, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1258, Illkirch, France"},{"name":"Universit\u00e9 de Strasbourg, Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn","family":"Laporte","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Illkirch, France"},{"name":"Centre National de la Recherche Scientifique, UMR7104, Illkirch, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1258, Illkirch, France"},{"name":"Universit\u00e9 de Strasbourg, Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda S","family":"Cowling","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Illkirch, France"},{"name":"Centre National de la Recherche Scientifique, UMR7104, Illkirch, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1258, Illkirch, France"},{"name":"Universit\u00e9 de Strasbourg, Illkirch, France"},{"name":"Dynacure, 67400 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,10,19]]},"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddz249\/30223934\/ddz249.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddz249\/30223934\/ddz249.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,19]],"date-time":"2019-10-19T03:59:10Z","timestamp":1571457550000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/advance-article\/doi\/10.1093\/hmg\/ddz249\/5599813"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,19]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddz249","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,19]]},"article-number":"ddz249"}}