{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:03:27Z","timestamp":1791119007842,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,7,27]],"date-time":"2004-07-27T00:00:00Z","timestamp":1090886400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2004,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Equine malignant hyperthermia (MH) has been suspected but never genetically confirmed. In this study, we investigated whether mutations in a candidate gene,<jats:italic>RyR1<\/jats:italic>, were associated with MH in two clinically affected horses.<jats:italic>RyR1<\/jats:italic>gene sequences revealed polymorphisms in exons 15, 17, and 46 in<jats:sub>WT<\/jats:sub>RyR1 and<jats:sub>MH<\/jats:sub>RyR1 horses with one derived amino acid change in<jats:sub>MH<\/jats:sub>RyR1 exon 46, R2454G. The<jats:sub>MH<\/jats:sub>RyR1 horses were genetically heterozygous for this mutation, but presented an MH phenotype with halothane challenge. Skeletal sarcoplasmic reticulum from a R2454G heterozygote collected during a fulminant MH episode showed significantly higher affinity and density of [<jats:sup>3<\/jats:sup>H]ryanodine\u2010binding sites compared to<jats:sub>WT<\/jats:sub>RyR1, but no differences in Ca<jats:sup>2+<\/jats:sup>, Mg<jats:sup>2+<\/jats:sup>, and caffeine modulation. In conclusion, an autosomal missense mutation in<jats:italic>RyR1<\/jats:italic>is associated with MH in the horse, providing a screening test for susceptible individuals. [<jats:sup>3<\/jats:sup>H]ryanodine\u2010binding analysis suggests that long\u2010lasting changes in RyR1 conformation persists in vitro after the triggering event. Muscle Nerve 30: 356\u2013365, 2004<\/jats:p>","DOI":"10.1002\/mus.20084","type":"journal-article","created":{"date-parts":[[2004,7,27]],"date-time":"2004-07-27T19:00:41Z","timestamp":1090954841000},"page":"356-365","source":"Crossref","is-referenced-by-count":87,"title":["Association of a mutation in the ryanodine receptor 1 gene with equine malignant hyperthermia"],"prefix":"10.1002","volume":"30","author":[{"given":"Monica","family":"Aleman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Riehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian M.","family":"Aldridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Lecouteur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey 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