{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:25:24Z","timestamp":1790429124427,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2019,5,2]],"date-time":"2019-05-02T00:00:00Z","timestamp":1556755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"M.I.U.R. P.R.I.N. 2015"},{"DOI":"10.13039\/501100008038","name":"NeRAB","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swiss Muscle Foundation (FSRMM)"},{"name":"OPO Stiftung"},{"name":"BOTNAR Stiftung"},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["SNF N\u00b0 31003A-169316"],"award-info":[{"award-number":["SNF N\u00b0 31003A-169316"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recessive ryanodine receptor 1 (RYR1) mutations cause congenital myopathies including multiminicore disease (MmD), congenital fiber-type disproportion and centronuclear myopathy. We created a mouse model knocked-in for the Q1970fsX16+A4329D RYR1 mutations, which are isogenic with those identified in a severely affected child with MmD. During the first 20\u00a0weeks after birth the body weight and the spontaneous running distance of the mutant mice were 20% and 50% lower compared to wild-type littermates. Skeletal muscles from mutant mice contained \u2018cores\u2019 characterized by severe myofibrillar disorganization associated with misplacement of mitochondria. Furthermore, their muscles developed less force and had smaller electrically evoked calcium transients. Mutant RyR1 channels incorporated into lipid bilayers were less sensitive to calcium and caffeine, but no change in single-channel conductance was observed. Our results demonstrate that the phenotype of the RyR1Q1970fsX16+A4329D compound heterozygous mice recapitulates the clinical picture of multiminicore patients and provide evidence of the molecular mechanisms responsible for skeletal muscle defects.<\/jats:p>","DOI":"10.1093\/hmg\/ddz092","type":"journal-article","created":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T03:20:47Z","timestamp":1556680847000},"page":"2987-2999","source":"Crossref","is-referenced-by-count":30,"title":["Quantitative RyR1 reduction and loss of calcium sensitivity of RyR1Q1970fsX16+A4329D cause cores and loss of muscle strength"],"prefix":"10.1093","volume":"28","author":[{"given":"Moran","family":"Elbaz","sequence":"first","affiliation":[{"name":"Departments of Anaesthesia and Biomedicine, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Departments 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