Knock-in mouse model of hypertrophic cardiomyopathy caused by troponin T mutation
| Project/Area Number |
24790791
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
DU Cheng-Kun 独立行政法人国立循環器病研究センター, 研究所, 研究員 (90590646)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肥大型心筋症 / ノックインマウス / 突然死 / 心筋トロポニンT / 遺伝子変異 / カルシウム感受性 / ノックイン / マウス / 発症メカニズム / 心筋トロポニン / ミューテーション / トロポニン / ノックインモデル |
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| Outline of Final Research Achievements |
We created knock-in mice with a missense mutation S179F in cardiac troponin T (cTnT), which had been found to be associated with human hypertrophic cardiomyopathy (HCM). Membrane-permeabilized cardiac muscle fibers from these mice showed significantly higher Ca2+ sensitivity in force generation than those from wild-type mice. The knock-in mice suffered from sudden death frequ ently, and histological examination of cardiac sections showed significant displacement fibrosis, myocardial hypertrophy, and myocyte disarray. Echocardiography showed that left ventricular (LV) end-diastolic dimension was significantly decreased with no changes in ejection fraction. In vivo cardiac catheter measurements showed a significant increase in LVdP/dtmin with no changes in LVdP/dtmax. These results indicate that the knock-in mouse with S179F mutation in cTnT is a useful mouse model of HCM closely capitulating the clinical phenotypes of human patients.
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Role of brain serotonin dysfunction in the pathophysiology of congestive heart failure2012
Author(s)
Li L, Morimoto S, Take S, Zhan D.-Y, Du C.-K, Wang Y.-Y, Fan X.-L, Yoshihara T, Takahashi-Yanaga F, Katafuchi T, Sasaguri T
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Journal Title
J Mol Cell Cardiol
Volume: 53
Issue: 6
Pages: 760-767
DOI
Related Report
Peer Reviewed
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