PUBLICATION

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

Authors
Ho, Y.L., Lin, Y.H., Tsai, W.Y., Hsieh, F.J., and Tsai, H.J.
ID
ZDB-PUB-090720-5
Date
2009
Source
Circulation journal : official journal of the Japanese Circulation Society   73(9): 1691-1697 (Journal)
Registered Authors
Tsai, Huai-Jen
Keywords
Antisense RNA, Cardiac troponin C, Dilated cardiomyopathy, Zebrafish
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Atrial Function/genetics
  • Base Sequence
  • Blotting, Western
  • Cardiac Myosins/genetics
  • Cardiomyopathy, Dilated/genetics*
  • Cardiomyopathy, Dilated/metabolism
  • Cardiomyopathy, Dilated/pathology
  • Cardiomyopathy, Dilated/physiopathology
  • Disease Models, Animal
  • Gene Knockdown Techniques*
  • Genotype
  • Green Fluorescent Proteins/biosynthesis
  • Green Fluorescent Proteins/genetics
  • Heart Rate/genetics
  • Molecular Sequence Data
  • Myocardial Contraction/genetics
  • Myocardium/metabolism
  • Myocardium/pathology
  • Myosin Light Chains/genetics
  • Phenotype
  • Promoter Regions, Genetic
  • RNA, Antisense/biosynthesis*
  • Stroke Volume/genetics
  • Transcription, Genetic
  • Troponin C/genetics*
  • Troponin C/metabolism
  • Ventricular Function/genetics
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
19609041 Full text @ Circ. J.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes