Conditional Antisense-Knockdown of Zebrafish Cardiac Troponin C as a New Animal Model for Dilated Cardiomyopathy

• Ho Yi-Lwun

  Graduate Institute of Clinical Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine

• Lin Yen-Hung

  Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine

• Tsai Wei-Yuan

  Institute of Molecular and Cellular Biology, National Taiwan University

• Hsieh Fong-Jou

  Department of Obstetrics and Gynecology, National Taiwan University Hospital and National Taiwan University College of Medicine

• Tsai Huai-Jen

  Institute of Molecular and Cellular Biology, National Taiwan University

Abstract

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. (Circ J 2009; 73: 1691-1697)<br>

Journal

• Circulation Journal

  Circulation Journal 73 (9), 1691-1697, 2009

  The Japanese Circulation Society

Keywords

• Antisense RNA
• Cardiac troponin C
• Dilated cardiomyopathy
• Zebrafish

Details

• CRID: 1390282680079868544
• NII Article ID: 10025935055
• NII Book ID: AA11591968
• DOI: 10.1253/circj.cj-09-0210
• ISSN: 13474820
• ISSN: 13469843
• Web Site: http://www.jstage.jst.go.jp/article/circj/73/9/73_CJ-09-0210/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2010041666
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed