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CASQ1 functions as both a Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010binding protein and a luminal regulator of ryanodine receptor (RYR1)\u2010mediated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release. Mice lacking skeletal CASQ1 are viable but exhibit reduced levels of releasable Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and altered contractile properties. Here we report that CASQ1\u2010null mice exhibit increased spontaneous mortality and susceptibility to heat\u2010and anesthetic\u2010induced sudden death. Exposure of CASQ1\u2010null mice to either 2% halo\u2010thane or heat stress triggers lethal episodes characterized by whole\u2010body contractures, elevated core temperature, and severe rhabdomyolysis, which are prevented by prior dantrolene administration. The characteristics of these events are remarkably similar to analogous episodes observed in humans with malignant hyperthermia (MH) and animal models of MH and environmental heat stroke (EHS).\n                    <jats:italic>In vitro<\/jats:italic>\n                    studies indicate that CASQ1\u2010null muscle exhibits increased contractile sensitivity to temperature and caffeine, temperature\u2010dependent increases in resting Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , and an increase in the magnitude of depolarization\u2010induced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release. These results demonstrate that CASQ1 deficiency alters proper control of RYR1 function and suggest CASQ1 as a potential candidate gene for linkage analysis in families with MH\/EHS where mutations in the RYR1 gene are excluded.\u2014Dainese, M.,Quarta, M., Lyfenko, A.D., Paolini, C., Canato, M., Reggiani, C., Dirksen, R.T., Protasi, F. Anesthetic\u2010and heat\u2010induced sudden death incalsequestrin\u20101\u2010knockout mice.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    23, 1710\u20131720 (2009)\n                  <\/jats:p>","DOI":"10.1096\/fj.08-121335","type":"journal-article","created":{"date-parts":[[2009,2,23]],"date-time":"2009-02-23T20:34:19Z","timestamp":1235421259000},"page":"1710-1720","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":105,"title":["Anesthetic\u2010and heat\u2010induced sudden death in calsequestrin\u20101\u2010knockout mice"],"prefix":"10.1096","volume":"23","author":[{"given":"Marco","family":"Dainese","sequence":"first","affiliation":[{"name":"Department of Basic and Applied Medical Sciences Centro Scienze dell'Invecchiamento Interuniversity Institute of Myology University G. d'Annunzio Chieti Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Quarta","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology Interuniversity Institute of Myology University of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alla D.","family":"Lyfenko","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Paolini","sequence":"additional","affiliation":[{"name":"Department of Basic and Applied Medical Sciences Centro Scienze dell'Invecchiamento Interuniversity Institute of Myology University G. d'Annunzio Chieti Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Canato","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology Interuniversity Institute of Myology University of Padova Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Reggiani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert T.","family":"Dirksen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feliciano","family":"Protasi","sequence":"additional","affiliation":[{"name":"Department of Basic and Applied Medical Sciences Centro Scienze dell'Invecchiamento Interuniversity Institute of Myology University G. d'Annunzio Chieti Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,23]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01774031"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01566.x"},{"key":"e_1_2_17_4_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.104.048447"},{"key":"e_1_2_17_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.68.6.1231"},{"key":"e_1_2_17_6_1","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/S0021-9258(18)33178-8","article-title":"Purification and characterization of calsequestrin from canine cardiac sarcoplasmic reticulum and identification of the 53,000 dalton glycoprotein","volume":"258","author":"Campbell K.P.","year":"1983","journal-title":"J. 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