{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:29:40Z","timestamp":1788881380547,"version":"build-2803163510"},"reference-count":46,"publisher":"The Company of Biologists","issue":"12","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR-10-IDEX-0002"],"award-info":[{"award-number":["ANR-10-IDEX-0002"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR-20-SFRI-0012"],"award-info":[{"award-number":["ANR-20-SFRI-0012"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR-17-EURE-0023"],"award-info":[{"award-number":["ANR-17-EURE-0023"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"name":"RYR1 Foundation","award":["RYR1-PoC"],"award-info":[{"award-number":["RYR1-PoC"]}]},{"DOI":"10.13039\/501100003768","name":"Universit\u00e9 de Strasbourg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003768","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Centronuclear myopathies (CNMs) are rare congenital muscle disorders with no effective treatment. Previous studies showed that tamoxifen improved muscle function in mice modeling CNMs caused by variants in MTM1, BIN1 and DNM2. Here, we investigated whether tamoxifen administration improves muscle function and pathology in the severe recessive Ryr1TM\/indel mouse model of RYR1-related CNM. Contractile performance, histological analyses and protein levels were assessed in Ryr1TM\/indel mice and control littermates (wild type) treated with either a tamoxifen-enriched diet (65\u2005mg\/kg of food) or a control diet for 5\u2005weeks, beginning at 3\u2005weeks of age. Ryr1TM\/indel mice displayed muscle weakness, reduced myofiber size and a high number of fibers with nuclei in abnormal position, regardless of the treatment. Force production during repeated contractions was reduced in tamoxifen-treated Ryr1TM\/indel mice compared to that in untreated Ryr1TM\/indel mice. The levels of CNM proteins (DNM2 and BIN1) were unchanged following the treatment. Tamoxifen did not improve muscle dysfunction, atrophy or histological hallmarks in Ryr1TM\/indel mice. Our data indicate that tamoxifen supplementation is not beneficial and may negatively impact muscle function in this model of CNM, suggesting limited therapeutic value for patients with RYR1 mutations.<\/jats:p>","DOI":"10.1242\/dmm.052462","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T10:44:11Z","timestamp":1767005051000},"source":"Crossref","is-referenced-by-count":2,"title":["Tamoxifen treatment fails to improve muscle dysfunction in a model of recessive\n                    <i>RYR1<\/i>\n                    -linked centronuclear myopathy"],"prefix":"10.1242","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8515-089X","authenticated-orcid":false,"given":"Charlotte","family":"Gineste","sequence":"first","affiliation":[{"name":"Department of Translational Medicine and Neurogenetics, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), Inserm U1258, Cnrs UMR7104, Strasbourg University , Illkirch 67404 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Reiss","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Neurogenetics, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), Inserm U1258, Cnrs UMR7104, Strasbourg University , Illkirch 67404 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8256-5862","authenticated-orcid":false,"given":"Jocelyn","family":"Laporte","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Neurogenetics, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), Inserm U1258, Cnrs UMR7104, Strasbourg University , Illkirch 67404 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"2025122905440421600_DMM052462C1","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1152\/physrev.00015.2007","article-title":"Skeletal muscle fatigue: cellular mechanisms","volume":"88","author":"Allen","year":"2008","journal-title":"Physiol. Rev."},{"key":"2025122905440421600_DMM052462C2","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/1750-1172-8-117","article-title":"Genotype-phenotype correlations in recessive RYR1-related myopathies","volume":"8","author":"Amburgey","year":"2013","journal-title":"Orphanet. J. Rare Dis."},{"key":"2025122905440421600_DMM052462C3","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.15252\/embj.201694613","article-title":"Membrane fission by dynamin: what we know and what we need to know","volume":"35","author":"Antonny","year":"2016","journal-title":"EMBO J."},{"key":"2025122905440421600_DMM052462C4","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1111\/j.1365-2990.2010.01149.x","article-title":"Recessive RYR1 mutations cause unusual congenital myopathy with prominent nuclear internalization and large areas of myofibrillar disorganization","volume":"37","author":"Bevilacqua","year":"2011","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"2025122905440421600_DMM052462C5","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1002\/ana.21235","article-title":"Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset","volume":"62","author":"Bitoun","year":"2007","journal-title":"Ann. Neurol."},{"key":"2025122905440421600_DMM052462C6","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1002\/humu.22067","article-title":"Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy","volume":"33","author":"Bohm","year":"2012","journal-title":"Hum. Mut."},{"key":"2025122905440421600_DMM052462C7","doi-asserted-by":"publisher","first-page":"3160","DOI":"10.1093\/brain\/awu272","article-title":"Adult-onset autosomal dominant centronuclear myopathy due to BIN1 mutations","volume":"137","author":"Bohm","year":"2014","journal-title":"Brain"},{"key":"2025122905440421600_DMM052462C8","doi-asserted-by":"publisher","first-page":"3024","DOI":"10.1093\/hmg\/ddz105","article-title":"Mouse model of severe recessive RYR1-related myopathy","volume":"28","author":"Brennan","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"2025122905440421600_DMM052462C9","doi-asserted-by":"publisher","first-page":"15060","DOI":"10.1073\/pnas.212498399","article-title":"The lipid phosphatase myotubularin is essential for skeletal muscle maintenance but not for myogenesis in mice","volume":"99","author":"Buj-Bello","year":"2002","journal-title":"Proc. Natl. Acad, Sci. USA"},{"key":"2025122905440421600_DMM052462C10","doi-asserted-by":"publisher","first-page":"2132","DOI":"10.1093\/hmg\/ddn112","article-title":"AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis","volume":"17","author":"Buj-Bello","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"2025122905440421600_DMM052462C11","doi-asserted-by":"publisher","first-page":"4615","DOI":"10.1113\/JP278235","article-title":"Fast skeletal muscle troponin activator CK-2066260 increases fatigue resistance by reducing the energetic cost of muscle contraction","volume":"597","author":"Cheng","year":"2019","journal-title":"J. Physiol."},{"key":"2025122905440421600_DMM052462C12","doi-asserted-by":"publisher","first-page":"e378","DOI":"10.1038\/emm.2017.208","article-title":"A focus on extracellular Ca(2+) entry into skeletal muscle","volume":"49","author":"Cho","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"2025122905440421600_DMM052462C13","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.bone.2019.03.033","article-title":"Aging of the musculoskeletal system: how the loss of estrogen impacts muscle strength","volume":"123","author":"Collins","year":"2019","journal-title":"Bone"},{"key":"2025122905440421600_DMM052462C14","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1172\/JCI71206","article-title":"Reducing dynamin 2 expression rescues X-linked centronuclear myopathy","volume":"124","author":"Cowling","year":"2014","journal-title":"J. Clin. Invest."},{"key":"2025122905440421600_DMM052462C15","doi-asserted-by":"publisher","first-page":"107","DOI":"10.2217\/fon.13.168","article-title":"Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy","volume":"10","author":"Cronin-Fenton","year":"2014","journal-title":"Future Oncol."},{"key":"2025122905440421600_DMM052462C16","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.ajpath.2012.10.018","article-title":"The anticancer drug tamoxifen counteracts the pathology in a mouse model of duchenne muscular dystrophy","volume":"182","author":"Dorchies","year":"2013","journal-title":"Am. J. Pathol."},{"key":"2025122905440421600_DMM052462C17","doi-asserted-by":"publisher","first-page":"4820","DOI":"10.1093\/hmg\/ddq413","article-title":"A centronuclear myopathy-dynamin 2 mutation impairs skeletal muscle structure and function in mice","volume":"19","author":"Durieux","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"2025122905440421600_DMM052462C18","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/nrm3266","article-title":"Dynamin, a membrane-remodelling GTPase","volume":"13","author":"Ferguson","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2025122905440421600_DMM052462C19","doi-asserted-by":"publisher","first-page":"4848","DOI":"10.1038\/s41467-018-07058-4","article-title":"Tamoxifen prolongs survival and alleviates symptoms in mice with fatal X-linked myotubular myopathy","volume":"9","author":"Gayi","year":"2018","journal-title":"Nat. Commun."},{"key":"2025122905440421600_DMM052462C20","doi-asserted-by":"publisher","first-page":"3029","DOI":"10.1093\/brain\/awac489","article-title":"Tamoxifen improves muscle structure and function of Bin1- and Dnm2-related centronuclear myopathies","volume":"146","author":"Gineste","year":"2023","journal-title":"Brain"},{"key":"2025122905440421600_DMM052462C21","doi-asserted-by":"publisher","first-page":"4158","DOI":"10.1093\/brain\/awad251","article-title":"MTM1 overexpression prevents and reverts BIN1-related centronuclear myopathy","volume":"146","author":"Giraud","year":"2023","journal-title":"Brain"},{"key":"2025122905440421600_DMM052462C22","doi-asserted-by":"publisher","first-page":"11377","DOI":"10.3390\/ijms222111377","article-title":"Common pathogenic mechanisms in centronuclear and myotubular myopathies and latest treatment advances","volume":"22","author":"Gomez-Oca","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2025122905440421600_DMM052462C23","doi-asserted-by":"publisher","first-page":"105375","DOI":"10.1016\/j.jsbmb.2019.105375","article-title":"Functions of estrogen and estrogen receptor signaling on skeletal muscle","volume":"191","author":"Ikeda","year":"2019","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"2025122905440421600_DMM052462C24","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1093\/jnci\/dji005","article-title":"CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment","volume":"97","author":"Jin","year":"2005","journal-title":"J. Natl. Cancer Inst."},{"key":"2025122905440421600_DMM052462C25","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.nmd.2007.01.016","article-title":"Centronuclear myopathy due to a de novo dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene","volume":"17","author":"Jungbluth","year":"2007","journal-title":"Neuromuscul. Disord."},{"key":"2025122905440421600_DMM052462C26","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/1750-1172-3-26","article-title":"Centronuclear (myotubular) myopathy","volume":"3","author":"Jungbluth","year":"2008","journal-title":"Orphanet. J. Rare Dis."},{"key":"2025122905440421600_DMM052462C27","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/nrneurol.2017.191","article-title":"Congenital myopathies: disorders of excitation-contraction coupling and muscle contraction","volume":"14","author":"Jungbluth","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"2025122905440421600_DMM052462C28","doi-asserted-by":"publisher","first-page":"272","DOI":"10.3390\/jpm13020272","article-title":"Pharmacokinetics of tamoxifen and its major metabolites and the effect of the african ancestry specific CYP2D6*17 variant on the formation of the active metabolite, endoxifen","volume":"13","author":"Kanji","year":"2023","journal-title":"J. Pers. Med."},{"key":"2025122905440421600_DMM052462C29","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1016\/j.omtm.2020.04.022","article-title":"Myostatin: a circulating biomarker correlating with disease in myotubular myopathy mice and patients","volume":"17","author":"Koch","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"2025122905440421600_DMM052462C30","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/ng0696-175","article-title":"A gene mutated in X\u2013linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast","volume":"13","author":"Laporte","year":"1996","journal-title":"Nat. Genet"},{"key":"2025122905440421600_DMM052462C31","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1126\/science.1071362","article-title":"Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle","volume":"297","author":"Lee","year":"2002","journal-title":"Science"},{"key":"2025122905440421600_DMM052462C32","doi-asserted-by":"publisher","first-page":"eaav1866","DOI":"10.1126\/scitranslmed.aav1866","article-title":"Amphiphysin 2 modulation rescues myotubular myopathy and prevents focal adhesion defects in mice","volume":"11","author":"Lionello","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"2025122905440421600_DMM052462C33","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1038\/gim.2012.108","article-title":"Laboratory testing of CYP2D6 alleles in relation to tamoxifen therapy","volume":"14","author":"Lyon","year":"2012","journal-title":"Genet. Med."},{"key":"2025122905440421600_DMM052462C45","doi-asserted-by":"publisher","first-page":"102507","DOI":"10.1016\/j.omtn.2025.102507","article-title":"microRNA-133a as an indicator of disease progression and treatment response in X-linked myotubular myopathy","volume":"36","author":"Maani","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"2025122905440421600_DMM052462C34","doi-asserted-by":"publisher","first-page":"4849","DOI":"10.1038\/s41467-018-07057-5","article-title":"Tamoxifen therapy in a murine model of myotubular myopathy","volume":"9","author":"Maani","year":"2018","journal-title":"Nat. Commun."},{"key":"2025122905440421600_DMM052462C35","doi-asserted-by":"publisher","first-page":"e137899","DOI":"10.1172\/jci.insight.137899","article-title":"Physiological impact and disease reversion for the severe form of centronuclear myopathy linked to dynamin","volume":"5","author":"Munoz","year":"2020","journal-title":"JCI Insight"},{"key":"2025122905440421600_DMM052462C36","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/j.nmd.2017.05.016","article-title":"Common and variable clinical, histological, and imaging findings of recessive RYR1-related centronuclear myopathy patients","volume":"27","author":"Neto","year":"2017","journal-title":"Neuromuscul. Disord."},{"key":"2025122905440421600_DMM052462C37","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1038\/ng2086","article-title":"Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy","volume":"39","author":"Nicot","year":"2007","journal-title":"Nat. Genet."},{"key":"2025122905440421600_DMM052462C46","doi-asserted-by":"publisher","first-page":"105339","DOI":"10.1016\/j.nmd.2025.105339","article-title":"Evaluation of dynamin 2 knockdown as a therapeutic strategy for RYR1 related myopathy","volume":"50","author":"Onofre-Oliveira","year":"2025","journal-title":"Neuromuscul. Disord."},{"key":"2025122905440421600_DMM052462C38","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1126\/science.1092586","article-title":"BAR domains as sensors of membrane curvature: the amphiphysin BAR structure","volume":"303","author":"Peter","year":"2004","journal-title":"Science"},{"key":"2025122905440421600_DMM052462C39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00421-010-1480-0","article-title":"Muscle fatigue: from observations in humans to underlying mechanisms studied in intact single muscle fibres","volume":"110","author":"Place","year":"2010","journal-title":"Eur. J. Appl. Physiol."},{"key":"2025122905440421600_DMM052462C40","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s10974-017-9470-z","article-title":"Physiology and pathophysiology of excitation-contraction coupling: the functional role of ryanodine receptor","volume":"38","author":"Santulli","year":"2017","journal-title":"J. Muscle Res. Cell Motil."},{"key":"2025122905440421600_DMM052462C41","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1016\/j.ymthe.2021.08.006","article-title":"Mice with muscle-specific deletion of Bin1 recapitulate centronuclear myopathy and acute downregulation of dynamin 2 improves their phenotypes","volume":"30","author":"Silva-Rojas","year":"2022","journal-title":"Mol. Ther."},{"key":"2025122905440421600_DMM052462C42","doi-asserted-by":"publisher","first-page":"eadk9167","DOI":"10.1126\/science.adk9167","article-title":"Dietary pro-oxidant therapy by a vitamin K precursor targets PI 3-kinase VPS34 function","volume":"386","author":"Swamynathan","year":"2024","journal-title":"Science"},{"key":"2025122905440421600_DMM052462C43","doi-asserted-by":"publisher","first-page":"15661","DOI":"10.1038\/ncomms15661","article-title":"Antisense oligonucleotide-mediated Dnm2 knockdown prevents and reverts myotubular myopathy in mice","volume":"8","author":"Tasfaout","year":"2017","journal-title":"Nat. Commun."},{"key":"2025122905440421600_DMM052462C44","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1002\/ana.22119","article-title":"RYR1 mutations are a common cause of congenital myopathies with central nuclei","volume":"68","author":"Wilmshurst","year":"2010","journal-title":"Ann. Neurol."}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.052462\/3678989\/dmm052462.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.052462\/3678989\/dmm052462.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T10:44:12Z","timestamp":1767005052000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/18\/12\/dmm052462\/370260\/Tamoxifen-treatment-fails-to-improve-muscle"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,1]]},"references-count":46,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.052462","relation":{},"ISSN":["1754-8403","1754-8411"],"issn-type":[{"value":"1754-8403","type":"print"},{"value":"1754-8411","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,1]]},"article-number":"dmm052462"}}