{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:20:15Z","timestamp":1791120015694,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2001,3,2]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014Although sarcomere protein gene mutations cause familial hypertrophic cardiomyopathy (FHC), individuals bearing a mutant cardiac\n            <jats:italic>myosin binding protein C<\/jats:italic>\n            (\n            <jats:italic>MyBP-C<\/jats:italic>\n            ) gene usually have a better prognosis than individuals bearing \u03b2\n            <jats:italic>-cardiac myosin heavy chain<\/jats:italic>\n            (MHC) gene mutations. Heterozygous mice bearing a cardiac MHC missense mutation (\u03b1MHC\n            <jats:sup>403\/+<\/jats:sup>\n            or a cardiac MyBP-C mutation (MyBP-C\n            <jats:sup>t\/+<\/jats:sup>\n            ) were constructed as murine FHC models using homologous recombination in embryonic stem cells. We have compared cardiac structure and function of these mouse strains by several methods to further define mechanisms that determine the severity of FHC. Both strains demonstrated progressive left ventricular (LV) hypertrophy; however, by age 30 weeks, \u03b1MHC\n            <jats:sup>403\/+<\/jats:sup>\n            mice demonstrated considerably more LV hypertrophy than MyBP-C\n            <jats:sup>t\/+<\/jats:sup>\n            mice. In older heterozygous mice, hypertrophy continued to be more severe in the \u03b1MHC\n            <jats:sup>403\/+<\/jats:sup>\n            mice than in the MyBP-C\n            <jats:sup>t\/+<\/jats:sup>\n            mice. Consistent with this finding, hearts from 50-week-old \u03b1MHC\n            <jats:sup>403\/+<\/jats:sup>\n            mice demonstrated increased expression of molecular markers of cardiac hypertrophy, but MyBP-C\n            <jats:sup>t\/+<\/jats:sup>\n            hearts did not demonstrate expression of these molecular markers until the mice were &gt;125 weeks old. Electrophysiological evaluation indicated that MyBP-C\n            <jats:sup>t\/+<\/jats:sup>\n            mice are not as likely to have inducible ventricular tachycardia as \u03b1MHC\n            <jats:sup>403\/+<\/jats:sup>\n            mice. In addition, cardiac function of \u03b1MHC\n            <jats:sup>403\/+<\/jats:sup>\n            mice is significantly impaired before the development of LV hypertrophy, whereas cardiac function of MyBP-C\n            <jats:sup>t\/+<\/jats:sup>\n            mice is not impaired even after the development of cardiac hypertrophy. Because these murine FHC models mimic their human counterparts, we propose that similar murine models will be useful for predicting the clinical consequences of other FHC-causing mutations. These data suggest that both electrophysiological and cardiac function studies may enable more definitive risk stratification in FHC patients.\n          <\/jats:p>","DOI":"10.1161\/01.res.88.4.383","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:52:16Z","timestamp":1339462336000},"page":"383-389","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":97,"title":["Comparison of Two Murine Models of Familial Hypertrophic Cardiomyopathy"],"prefix":"10.1161","volume":"88","author":[{"given":"Bradley K.","family":"McConnell","sequence":"first","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Fatkin","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Semsarian","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen A.","family":"Jones","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Georgakopoulos","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin T.","family":"Maguire","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Healey","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James O.","family":"Mudd","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan P. G.","family":"Moskowitz","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Conner","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Giewat","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Wakimoto","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles I.","family":"Berul","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick J.","family":"Schoen","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Kass","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E.","family":"Seidman","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. G.","family":"Seidman","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division and Howard Hughes Medical Institute (D.F., C.E.S.), Brigham and Women\u2019s Hospital, Boston, Mass; Department of Genetics (B.K.M., C.S., K.A.J., M.J.H., J.O.M., D.A.C., M.G., J.G.S.), Howard Hughes Medical Institute and Harvard Medical School, Boston Mass; Division of Cardiology (D.G., D.A.K.), Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Md; Department of Cardiology (C.T.M., H.W., C.I.B.), Children\u2019s Hospital and Department of Pediatrics,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","unstructured":"Hunter JJ Grace A Chien KR. Molecular and cellular biology of cardiac hypertrophy and failure. In: Chien KR ed. Molecular Basis of Cardiovascular Disease. Philadelphia Pa: Saunders; 1999:211\u2013250."},{"key":"e_1_3_2_2_2","unstructured":"Fatkin D Seidman JG Seidman CE. Hypertrophic cardiomyopathy. In: Willerson JT Cohn JN eds. Cardiovascular Medicine. Philadelphia Pa: Saunders; 2000:1055\u20131074."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(81)90068-0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(83)80269-1"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s003950050196"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199204233261703"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199804303381802"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.97.22.2230"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401640"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI3880"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5262.731"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/6549"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1940"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7377"},{"key":"e_1_3_2_15_2","unstructured":"Berul CI Mendelsohn ME. Molecular biology and genetics of cardiac disease associated with sudden death: electrophysiologic studies in mouse models of inherited diseases. In: Estes NAM Salem DN Wang PJ eds. Sudden Cardiac Death in the Athlete. Armonk NY: Futura Publishing Co; 1998:465\u2013481."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4631"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.70.5.812"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.94.10.2641"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119197"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.274.2.H385"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)42067-9"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018613907574"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117795"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.84.4.475"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5220"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(87)90399-7"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.eurheartj.a062472"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1295-434"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.RES.88.4.383","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T20:48:11Z","timestamp":1715546891000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.RES.88.4.383"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,3,2]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2001,3,2]]}},"alternative-id":["10.1161\/01.RES.88.4.383"],"URL":"https:\/\/doi.org\/10.1161\/01.res.88.4.383","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,3,2]]},"assertion":[{"value":"2001-03-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}