Deletion of Pr72 causes cardiac developmental defects in Zebrafish
| Autor: | Sufang Dong, Yanggan Wang, Zhan Yin, Jun Wan, Zhu-liang Huang, Xuedong Gan, Jie Yang, Fang Zheng, Xiaowen Chen, Guibo Song, Ming Yan, Han Mingjun, Zuhua Li |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genome engineering Embryology lcsh:Medicine Engineering and technology Synthetic genome editing Animals Genetically Modified Gene Knockout Techniques Myofibrils Cell Signaling Animal Cells Medicine and Health Sciences Myocyte Heart looping Myocytes Cardiac Synthetic bioengineering Protein Phosphatase 2 Cardiac Atria lcsh:Science Zebrafish Wnt Signaling Pathway WNT Signaling Cascade Multidisciplinary Wnt signaling pathway Eukaryota Heart Animal Models Signaling Cascades Cell biology TALENs Experimental Organism Systems Osteichthyes Vertebrates Phosphorylation Anatomy Cellular Types Research Article Signal Transduction Sarcomeres Heart Defects Congenital Cardiac Ventricles Protein subunit Muscle Tissue Bioengineering Biology Research and Analysis Methods 03 medical and health sciences Model Organisms Animals Humans Synthetic biology Muscle Cells 030102 biochemistry & molecular biology Myocardium lcsh:R Embryos Synthetic genomics Wild type Organisms Biology and Life Sciences Protein phosphatase 2 Cell Biology Zebrafish Proteins biology.organism_classification Disease Models Animal 030104 developmental biology Fish Biological Tissue Animal Studies Cardiovascular Anatomy lcsh:Q Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 13, Iss 11, p e0206883 (2018) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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