Conditional antisense-knockdown of zebrafish cardiac troponin C as a new animal model for dilated cardiomyopathy.
BACKGROUND
Mutations of cardiac troponin C (cTnC) can cause dilated cardiomyopathy in humans.


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.
Ho
Yi-Lwun
YL
Graduate Institute of Clinical Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Lin
Yen-Hung
YH
Tsai
Wei-Yuan
WY
Hsieh
Fong-Jou
FJ
Tsai
Huai-Jen
HJ
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D016275:Atrial Function / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D024722:Cardiac Myosins / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006339:Heart Rate / Q000235:genetics; D008969:Molecular Sequence Data; D009200:Myocardial Contraction / Q000235:genetics; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018994:Myosin Light Chains / Q000235:genetics; D010641:Phenotype; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense / Q000096:biosynthesis*; D013318:Stroke Volume / Q000235:genetics; D014158:Transcription, Genetic; D019209:Troponin C / Q000235:genetics* / Q000378:metabolism; D016276:Ventricular Function / Q000235:genetics; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
D018994:Myosin Light Chains; D016372:RNA, Antisense; D019209:Troponin C; D029961:Zebrafish Proteins; C107184:myosin light chain 2; D049452:Green Fluorescent Proteins; D024722:Cardiac Myosins