Conditional antisense-knockdown of zebrafish cardiac troponin C as a new animal model for dilated cardiomyopathy.

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.

• Authors: Yi-Lwun Ho, Yen-Hung Lin, Wei-Yuan Tsai, Fong-Jou Hsieh, Huai-Jen Tsai
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 73 Issue 9 Pg. 1691-7 (Sep 2009) ISSN: 1347-4820 [Electronic] Japan
• PMID: 19609041 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Myosin Light Chains
• RNA, Antisense
• Troponin C
• Zebrafish Proteins
• myosin light chain 2
• Green Fluorescent Proteins
• Cardiac Myosins

Topics

• Amino Acid Sequence
• Animals
• Animals, Genetically Modified
• Atrial Function (genetics)
• Base Sequence
• Blotting, Western
• Cardiac Myosins (genetics)
• Cardiomyopathy, Dilated (genetics, metabolism, pathology, physiopathology)
• Disease Models, Animal
• Gene Knockdown Techniques
• Genotype
• Green Fluorescent Proteins (biosynthesis, genetics)
• Heart Rate (genetics)
• Molecular Sequence Data
• Myocardial Contraction (genetics)
• Myocardium (metabolism, pathology)
• Myosin Light Chains (genetics)
• Phenotype
• Promoter Regions, Genetic
• RNA, Antisense (biosynthesis)
• Stroke Volume (genetics)
• Transcription, Genetic
• Troponin C (genetics, metabolism)
• Ventricular Function (genetics)
• Zebrafish (genetics)
• Zebrafish Proteins (genetics, metabolism)