PUBLICATION
Deletion of Pr72 causes cardiac developmental defects in Zebrafish
- Authors
- Song, G., Han, M., Li, Z., Gan, X., Chen, X., Yang, J., Dong, S., Yan, M., Wan, J., Wang, Y., Huang, Z., Yin, Z., Zheng, F.
- ID
- ZDB-PUB-181128-5
- Date
- 2018
- Source
- PLoS One 13: e0206883 (Journal)
- Registered Authors
- Gan, Xuedong, Li, Zuhua, Yin, Zhan, Zheng, Fang
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Disease Models, Animal
- Gene Knockout Techniques
- Heart/growth & development*
- Heart Defects, Congenital/genetics*
- Humans
- Myocardium/cytology
- Myocardium/metabolism
- Myocardium/pathology
- Myocytes, Cardiac/metabolism
- Myocytes, Cardiac/pathology
- Protein Phosphatase 2/genetics*
- Wnt Signaling Pathway/genetics*
- Zebrafish
- Zebrafish Proteins/genetics*
- PubMed
- 30481179 Full text @ PLoS One
Citation
Song, G., Han, M., Li, Z., Gan, X., Chen, X., Yang, J., Dong, S., Yan, M., Wan, J., Wang, Y., Huang, Z., Yin, Z., Zheng, F. (2018) Deletion of Pr72 causes cardiac developmental defects in Zebrafish. PLoS One. 13:e0206883.
Abstract
The alpha regulator subunit B'' of protein phosphatase 2 (PPP2R3A), a regulatory subunit of protein phosphatase 2A (PP2A), was reported to present a special subcellular localization in cardiomyocytes and elevate in non-ischemia failing hearts. PPP2R3A has two transcriptions PR72 and PR130. PR72 acts as a negative regulator of the Wnt signaling cascade, while the Wnt signaling cascade plays a pivotal role in cardiac development. And PR130 was found to be involved in cardiac development of zebrafish in our previous study. Thus, to investigate the function of PR72 in heart, two stable pr72 knockout (KO) zebrafish lines were generated using Transcription Activator-Like Effector Nuclease (TALEN) technology. Homozygous pr72 KO fish struggled to survive to adulthood and exhibited cardiac developmental defects, including enlarged ventricular chambers, reduced cardiomyocytes and decreased cardiac function. And the defective sarcomere ultrastructure that affected mitochondria, I bands, Z lines, and intercalated disks was also observed. Furthermore, the abnormal heart looping was detected in mutants which could be rescued by injection with wild type pr72 mRNA. Additionally, it was found that Wnt effectors were elevated in mutants. Those indicated that deletion of pr72 in zebrafish interrupted cardiac development, probably through activation of the Wnt pathway.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping