PUBLICATION
Heart-targeted overexpression of Nip3a in zebrafish embryos causes abnormal heart development and cardiac dysfunction
- Authors
- Wang, W.D., Huang, C.J., Lu, Y.F., Hsin, J.P., Prabhakar, V.R., Cheng, C.F., and Hwang, S.P.
- ID
- ZDB-PUB-060724-23
- Date
- 2006
- Source
- Biochemical and Biophysical Research Communications 347(4): 979-987 (Journal)
- Registered Authors
- Huang, Chang-Jen, Hwang, Sheng-Ping L., Wang, Wen-Der
- Keywords
- Nip3a, Apoptosis, Zebrafish, Heart dysfunction, Endocardial cushion formation, Atrioventricular canal, Myocardium cell death
- MeSH Terms
-
- Animals
- Apoptosis/physiology
- Bone Morphogenetic Protein 4
- Bone Morphogenetic Proteins/genetics
- Bone Morphogenetic Proteins/pharmacology
- Gene Expression Regulation, Developmental/physiology
- Heart/embryology*
- Heart Defects, Congenital/genetics
- Heart Defects, Congenital/pathology
- Promoter Regions, Genetic/physiology
- Zebrafish/embryology
- Zebrafish Proteins/biosynthesis
- Zebrafish Proteins/genetics*
- PubMed
- 16854375 Full text @ Biochem. Biophys. Res. Commun.
Citation
Wang, W.D., Huang, C.J., Lu, Y.F., Hsin, J.P., Prabhakar, V.R., Cheng, C.F., and Hwang, S.P. (2006) Heart-targeted overexpression of Nip3a in zebrafish embryos causes abnormal heart development and cardiac dysfunction. Biochemical and Biophysical Research Communications. 347(4):979-987.
Abstract
We transiently expressed a proapoptotic protein, Nip3a, by a heart-specific BMP4 promoter in zebrafish embryos and generated two variants of embryos with abnormal heart phenotypes (A and B). Embryos with phenotype A heart defects showed hypoplastic or elongated ventricles, elongated or enlarged atriums with no normal cardiac looping resulting a significant longer SV-BA distance, and bradycardia at 48 h post-fertilization (hpf). Embryos with phenotype B heart defects showed an enlarged fluid-filled pericardium, severe hypoplasia, non-contracting ventricles, and elongated or enlarged slowly beating atriums with no normal looping. Histological sections further revealed the absence of a proper atrioventricular boundary and no endocardial cells lining this region in both 48- and 72-hpf Nip3a-overexpressing embryos, implicating defective endocardial cushion formation. These phenotypes are reminiscent of atrioventricular canal defects in humans. In addition, induced apoptotic myocardium cells were clustered in the presumptive atrioventricular boundary as well as in the adjacent ventricle and atrium of 48- and 72-hpf Nip3a-overexpressing embryos. Nip3a expression was readily detected in 80% epiboly BMP4-Nip3a-injected embryos, and defects in heart development were observed in both the linear heart tube and subsequent chamber formation stages. These results showed that myocyte apoptosis is a universal pathogenic factor for congenital heart failure using zebrafish as a model organism.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping