Conditional Antisense-Knockdown of Zebrafish Cardiac Troponin C as a New Animal Model for Dilated Cardiomyopathy
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概要
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Background: Mutations of cardiac troponin C (cTnC) can cause dilated cardiomyopathy in humans. Methods and Results: Plasmids were constructed such that the reverse tetracycline-controlled transactivator (rtTA) was driven by the cardiac myosin light chain 2 promoter. This heart-specific rtTA bound another bidirectional promoter to express the green fluorescence protein reporter gene and the antisense RNA of cTnC in the presence of doxycycline. A transgenic line of zebrafish (CA17) with cTnC dysfunction was also generated. The heart rates of the embryos in the CA17 line were significantly slower than those of embryos in the control T03 transgenic line at 6 and 12 days post fertilization (dpf). In the CA17 line, cardiac chambers in the F2 embryos were significantly greater and the ventricular ejection fraction was lower than those in the T03 at both 6 and 12 dpf. The mortality rate of F2 adult fish of the CA17 line was also significantly higher (P<0.001). Conclusions: Using conditional expression of antisense RNA of zebrafish cTnC, a new animal model with phenotypes simulating dilated cardiomyopathy has been created.
- 2009-08-20
著者
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Ho Yi-lwun
Graduate Institute Of Clinical Medicine National Taiwan University Hospital And National Taiwan Univ
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Tsai Wei-yuan
Institute Of Molecular And Cellular Biology National Taiwan University
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LIN Yen-Hung
Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and Nat
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HSIEH Fong-Jou
Department of Obstetrics and Gynecology, National Taiwan University Hospital and National Taiwan Uni
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TSAI Huai-Jen
Institute of Molecular and Cellular Biology, National Taiwan University
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Lin Yen-hung
Division Of Cardiology Department Of Internal Medicine National Taiwan University Hospital And Natio
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Hsieh Fong-jou
Department Of Obstetrics And Gynecology National Taiwan University Hospital And National Taiwan Univ
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Tsai Huai-jen
Institute Of Molecular And Cellular Biology National Taiwan University
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Tsai Huai-jen
Institute Of Fisheries Science National Taiwan University
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- Conditional Antisense-Knockdown of Zebrafish Cardiac Troponin C as a New Animal Model for Dilated Cardiomyopathy
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