{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:44:44Z","timestamp":1791431084861,"version":"4.3.3"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"33","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,8,17]]},"abstract":"<jats:p>\n                    Mutations in the\n                    <jats:italic>MTM1<\/jats:italic>\n                    gene encoding myotubularin cause X-linked myotubular myopathy (XLMTM), a well-defined subtype of human centronuclear myopathy. Seven male Labrador Retrievers, age 14\u201326 wk, were clinically evaluated for generalized weakness and muscle atrophy. Muscle biopsies showed variability in fiber size, centrally placed nuclei resembling fetal myotubes, and subsarcolemmal ringed and central dense areas highlighted with mitochondrial specific reactions. Ultrastructural studies confirmed the centrally located nuclei, abnormal perinuclear structure, and mitochondrial accumulations. Wild-type triads were infrequent, with most exhibiting an abnormal orientation of T tubules.\n                    <jats:italic>MTM1<\/jats:italic>\n                    gene sequencing revealed a unique exon 7 variant in all seven affected males, causing a nonconservative missense change, p.N155K, which haplotype data suggest derives from a recent founder in the local population. Analysis of a worldwide panel of 237 unaffected Labrador Retrievers and 59 additional control dogs from 25 other breeds failed to identify this variant, supporting it as the pathogenic mutation. Myotubularin protein levels and localization were abnormal in muscles from affected dogs, and expression of GFP-MTM1 p.N155K in COS-1 cells showed that the mutant protein was sequestered in proteasomes, where it was presumably misfolded and prematurely degraded. These data demonstrate that XLMTM in Labrador Retrievers is a faithful genetic model of the human condition.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1003677107","type":"journal-article","created":{"date-parts":[[2010,8,3]],"date-time":"2010-08-03T22:19:36Z","timestamp":1280873976000},"page":"14697-14702","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":128,"title":["<i>MTM1<\/i>\n                    mutation associated with X-linked myotubular myopathy in Labrador Retrievers"],"prefix":"10.1073","volume":"107","author":[{"given":"Alan H.","family":"Beggs","sequence":"first","affiliation":[{"name":"Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease Research at Children's Hospital Boston and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"B\u00f6hm","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Genetics, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U964, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 7104, Universit\u00e9 de Strasbourg, Coll\u00e8ge de France, Chaire de G\u00e9n\u00e9tique Humaine, 67400 Illkirch, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Snead","sequence":"additional","affiliation":[{"name":"Western College of Veterinary Medicine, University of Saskatchewan, SK, Canada S7N 5B4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Kozlowski","sequence":"additional","affiliation":[{"name":"Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease Research at Children's Hospital Boston and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Maurer","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche 955, G\u00e9n\u00e9tique Fonctionnelle et M\u00e9dicale, Institut National de la Recherche Agronomique, Universit\u00e9 Paris-Est, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, 94700 Maisons-Alfort, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Minor","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin K.","family":"Childers","sequence":"additional","affiliation":[{"name":"Wake Forest University Health Sciences, Winston-Salem, NC 27157;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Western College of Veterinary Medicine, University of Saskatchewan, SK, Canada S7N 5B4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Hitte","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 6061, Universit\u00e9 de Rennes 1, F-35000 Rennes, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Mickelson","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling T.","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California at San Diego, La Jolla, CA 92093; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Mizisin","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California at San Diego, La Jolla, CA 92093; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Buj-Bello","sequence":"additional","affiliation":[{"name":"G\u00e9n\u00e9thon, 91000 Evry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Tiret","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche 955, G\u00e9n\u00e9tique Fonctionnelle et M\u00e9dicale, Institut National de la Recherche Agronomique, Universit\u00e9 Paris-Est, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, 94700 Maisons-Alfort, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn","family":"Laporte","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Genetics, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U964, Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 7104, Universit\u00e9 de Strasbourg, Coll\u00e8ge de France, Chaire de G\u00e9n\u00e9tique Humaine, 67400 Illkirch, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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