{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:14:56Z","timestamp":1791029696872,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,11,30]],"date-time":"2011-11-30T00:00:00Z","timestamp":1322611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1P01 AR52354\u201005"],"award-info":[{"award-number":["1P01 AR52354\u201005"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["3R01 AR043140\u201015"],"award-info":[{"award-number":["3R01 AR043140\u201015"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01 ES014901"],"award-info":[{"award-number":["1R01 ES014901"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p>\n                    Mutation T4825I in the type 1 ryanodine receptor (RYR1\n                    <jats:sup>T4825I\/+<\/jats:sup>\n                    ) confers human malignant hyperthermia susceptibility (MHS). We report a knock\u2010in mouse line that expresses the isogenetic mutation T4826I. Heterozygous RYR1\n                    <jats:sup>T4826I\/+<\/jats:sup>\n                    (Het) or homozygous RYR1\n                    <jats:sup>T4826I\/T4826I<\/jats:sup>\n                    (Hom) mice are fully viable under typical rearing conditions but exhibit genotype\u2010and sex\u2010dependent susceptibility to environmental conditions that trigger MH. Hom mice maintain higher core temperatures than WT in the home cage, have chronically elevated myoplasmic[Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>rest<\/jats:sub>\n                    , and present muscle damage in soleus with a strong sex bias. Mice subjected to heat stress in an enclosed 37\u00b0C chamber fail to trigger MH regardless of genotype, whereas heat stress at 41\u00b0C invariably triggers fulminant MH in Hom, but not Het, mice within 20 min. WT and Het female mice fail to maintain euthermic body temperature when placed atop a bed whose surface is 37\u00b0C during halo\u2010thane anesthesia (1.75%) and have no hyperthermic response, whereas 100% Hom mice of either sex and 17% of the Het males develop fulminant MH. WT mice placed on a 41\u00b0C bed maintain body temperature while being administered halothane, and 40% of the Het females and 100% of the Het males develop fulminant MH within 40 min. Myopathic alterations in soleus were apparent by 12 mo, including abnormally distributed and enlarged mitochondria, deeply infolded sarcolemma, and frequent \u2217\u2217\u2217\n                    <jats:italic>Z<\/jats:italic>\n                    \u2010line streaming regions, which were more severe in males. These data demonstrate that an MHS mutation within the\n                    <jats:italic>S4\u2010S<\/jats:italic>\n                    5\u2217\u2217\u2217 cytoplasmic linker of RYR1 confers genotype\u2010 and sex\u2010dependent susceptibility to pharmacological and environmental stressors that trigger fulminant MH and promote myopathy.\u2014Yuen, B., Boncompagni, S., Feng, W., Yang, T., Lopez, J. R., Matthaei, K. I., Goth, S. R., Protasi, F., Franzini\u2010Armstrong, C., Allen, P. D., Pessah, I. N. Mice expressing T4826I\u2010RYR1 are viable but exhibit sex\u2010 and genotype\u2010dependent susceptibility to malignant hyperthermia and muscle damage.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 1311\u20101322 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-197582","type":"journal-article","created":{"date-parts":[[2011,12,2]],"date-time":"2011-12-02T05:23:36Z","timestamp":1322803416000},"page":"1311-1322","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Mice expressing T4826I\u2010RYR1 are viable but exhibit sex\u2010 and genotype\u2010dependent susceptibility to malignant hyperthermia and muscle damage"],"prefix":"10.1096","volume":"26","author":[{"given":"Benjamin","family":"Yuen","sequence":"first","affiliation":[{"name":"Department of Veterinary Molecular Biosciences University of California Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Boncompagni","sequence":"additional","affiliation":[{"name":"Center for Research on Aging and Department of Neuroscience and Imaging University of G. d'Annunzio Chieti Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Veterinary Molecular Biosciences University of California Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianzhong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose R.","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus I.","family":"Matthaei","sequence":"additional","affiliation":[{"name":"John Curtin School of Medical Research Australian National University Canberra Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel R.","family":"Goth","sequence":"additional","affiliation":[{"name":"Department of Veterinary Molecular Biosciences University of California Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feliciano","family":"Protasi","sequence":"additional","affiliation":[{"name":"Center for Research on Aging and Department of Neuroscience and Imaging University of G. d'Annunzio Chieti Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Franzini\u2010Armstrong","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac N.","family":"Pessah","sequence":"additional","affiliation":[{"name":"Department of Veterinary Molecular Biosciences University of California Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,11,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-443-06959-8.00037-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-002-0871-5"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3182320068"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0b013e3181a7c8e5"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.293.23.2918"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20356"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0b013e3181ac1548"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)03078-5"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aep204"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/369556a0"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/380072a0"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.11.7360"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-10-104"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.140.4.831"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1341.007"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200612000-00016"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4497fje"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.110.067959"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.043299"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.02.042"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812661106"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200910329"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911496106"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.153247"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201010523"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912126106"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.012688999"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.10.1515"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3181d69283"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199703000-00014"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/87.2.240"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21397"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200211000-00007"},{"key":"e_1_2_7_35_1","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1242\/dev.120.6.1651","article-title":"Expression and methylation of imprinted genes during in vitro differentiation of mouse parthenogenetic and androgenetic embryonic stem cell lines","volume":"120","author":"Szabo P.","year":"1994","journal-title":"Development"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.10.3518-3526.2002"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1526-968X(200002)26:2<116::AID-GENE4>3.0.CO;2-X"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018380108"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.107300"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/61.10.995"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E08-07-0783"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2010.00623.x"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.16.11618"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.2741\/A803"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.119.1.15"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00415.2004"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408375200"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.194316"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09471"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.171967"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.37.25971"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000085"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116269"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116270"},{"key":"e_1_2_7_55_1","doi-asserted-by":"crossref","first-page":"511a","DOI":"10.1016\/j.bpj.2009.12.2780","article-title":"Enhanced RyR1 channel activity by the knock\u2010in mouse that expresses human malignant hyperthermia mutation T4826I","volume":"98","author":"Feng W.","year":"2010","journal-title":"Biophys. J."},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(83)90058-8"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092380304"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm096"}],"updated-by":[{"DOI":"10.1096\/fj.11-197582err","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000}}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.11-197582","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.11-197582","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.11-197582","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T19:02:14Z","timestamp":1761678134000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.11-197582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11,30]]},"references-count":57,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012,3]]}},"alternative-id":["10.1096\/fj.11-197582"],"URL":"https:\/\/doi.org\/10.1096\/fj.11-197582","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,11,30]]},"assertion":[{"value":"2011-10-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-11-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-11-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}