{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T20:45:59Z","timestamp":1781383559696,"version":"3.54.1"},"reference-count":67,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":41,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Interdisciplinary Thematic Institute IMCBio+","award":["ANR-10-IDEX-0002,ANR-20-SFRI-0012,ANR-17-EURE-0023"],"award-info":[{"award-number":["ANR-10-IDEX-0002,ANR-20-SFRI-0012,ANR-17-EURE-0023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,24]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>MTM1<\/jats:italic>\n                    gene encodes myotubularin (MTM1), a phosphatidylinositol 3-phosphate [PI(3)P] lipid phosphatase. Loss-of-function mutations in\n                    <jats:italic>MTM1<\/jats:italic>\n                    cause X-linked myotubular myopathy (XLMTM), a severe congenital myopathy with no available cure and a poorly understood pathomechanism. The importance of MTM1 enzymatic activity and its PI(3)P substrate in physiology under normal conditions and in XLMTM is unclear. We generated the\n                    <jats:italic>Mtm1-<\/jats:italic>\n                    KI C375S mice in which the endogenous MTM1 was converted to a phosphatase-dead protein. Mutant mice survived a median of 12 weeks and demonstrated progressively impaired motor skills. Observed muscle hypotrophy and reduced force production compared with their WT littermates (~3.9-fold reduction in absolute maximal force) were responsible for these severe phenotypes. A significantly higher level of PI(3)P was found in the muscle of\n                    <jats:italic>Mtm1-<\/jats:italic>\n                    KI C375S mice. Muscle histology and molecular characterization revealed XLMTM hallmarks, with (a) alteration of the mTOR and autophagy pathways correlating with muscle hypotrophy and (b) abnormal myofiber intracellular organization correlating with impaired muscle force. Overall, this study reveals the importance of MTM1 phosphatase activity and related PI(3)P substrate for postnatal muscle maintenance, and it highlights the significance of MTM1 phosphatase activity in the development of X-linked myotubular myopathy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.189286","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T16:00:26Z","timestamp":1760457626000},"source":"Crossref","is-referenced-by-count":1,"title":["Lack of myotubularin phosphatase activity is the main cause of X-linked myotubular myopathy"],"prefix":"10.1172","volume":"10","author":[{"given":"Foteini","family":"Moschovaki-Filippidou","sequence":"first","affiliation":[{"name":"IGBMC (Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire), Inserm UMR-S 1258, CNRS UMR7104, Universit\u00e9 de Strasbourg, F67404 Illkirch, 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