{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:10:18Z","timestamp":1790788218465,"version":"4.1.0"},"reference-count":36,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2015,9,21]],"date-time":"2015-09-21T00:00:00Z","timestamp":1442793600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neuromuscular Diseases"],"published-print":{"date-parts":[[2015,9,21]]},"abstract":"<jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Central Core Disease (CCD) is a congenital myopathy often resulting from a mutation in\n                      <jats:italic>RYR1<\/jats:italic>\n                      gene. Mutations in RyR1 can increase or decrease channel activity, or induce a reduction in the amount of protein. The consequences of a single mutation are sometimes multiple and the analysis of the functional effects is complex.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The consequences of the p.Y4864H mutation identified in a CCD patient have been studied regarding both RyR1 function and amount.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>The amount of RyR1 in human and mouse muscles was evaluated using qRT-PCR and quantitative Western blot, and calcium release was studied using calcium imaging on primary cultures. The results were compared between human and mouse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The p.Y4864H mutation induced an alteration of calcium release, and in addition was associated to a reduction in the amount of RyR1 in the patient\u2019s muscle. This suggests two possible pathophysiological mechanisms: the alteration of calcium release could result from a modification of the channel properties of RyR1 or from a RyR1 reduction. In order to discriminate between the two hypotheses, we used the heterozygous RyR1 knockout (RyR1\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                      ) mouse model showing a comparable RyR1 protein reduction. No reduction in calcium release was observed in primary muscle culture from these mice, and no muscle weakness was measured.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Because the reduction in the amount of RyR1 protein has no functional consequences in the murine model, the muscle weakness observed in the patient is most likely the result of a modification of the calcium channel function of RyR1 due to the p.Y4864H mutation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jnd-150073","type":"journal-article","created":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T08:38:42Z","timestamp":1448613522000},"page":"421-432","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":24,"title":["Functional Characterization of a Central Core Disease RyR1 Mutation (p.Y4864H) Associated with Quantitative Defect in RyR1 Protein"],"prefix":"10.1177","volume":"2","author":[{"given":"Marine","family":"Cacheux","sequence":"first","affiliation":[{"name":"INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France"},{"name":"Universit\u00e9 Joseph Fourier, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Blum","sequence":"additional","affiliation":[{"name":"INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France"},{"name":"Universit\u00e9 Joseph Fourier, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"S\u00e9bastien","sequence":"additional","affiliation":[{"name":"INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France"},{"name":"Universit\u00e9 Joseph Fourier, Grenoble, 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