Deletion of Pr72 causes cardiac developmental defects in Zebrafish.
Deletion of Pr72 causes cardiac developmental defects in Zebrafish.
复制标题
Pr72 的缺失会导致斑马鱼心脏发育缺陷。
DOI：
10.1371/journal.pone.0206883
复制
发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Zheng F
中科院分区：
文献类型：
--
作者：
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
蛋白磷酸酶2 （PPP2R3A）的α调节亚基B”是蛋白磷酸酶2A （PP2A）的调节亚基，据报道在心肌细胞中表现出特殊的亚细胞定位，并在非缺血衰竭心脏中升高。PPP2R3A有两个转录PR72和PR130。PR72作为Wnt信号级联的负调控因子，而Wnt信号级联在心脏发育中起关键作用。在我们之前的研究中发现PR130参与了斑马鱼的心脏发育。因此，为了研究PR72在心脏中的功能，使用转录激活因子样效应核酸酶（TALEN）技术生成了两个稳定的PR72敲除（KO）斑马鱼系。纯合子pr72 KO鱼很难存活到成年，并表现出心脏发育缺陷，包括心室增大、心肌细胞减少和心功能下降。观察到缺陷肌节超微结构对线粒体、I带、Z线、插盘的影响。此外，在注射野生型pr72 mRNA可挽救的突变体中检测到异常的心脏环。此外，我们还发现Wnt效应物在突变体中升高。这些研究表明，斑马鱼中pr72的缺失可能通过激活Wnt通路来中断心脏发育。
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.
登录
查看更多内容
影响因子：
11
作者：
Durak O;de Anda FC;Singh KK;Leussis MP;Petryshen TL;Sklar P;Tsai LH
通讯作者：
Tsai LH
影响因子：
5
作者：
Ranieri A;Kemp E;Burgoyne JR;Avkiran M
通讯作者：
Avkiran M
影响因子：
5
作者：
Lubbers ER;Mohler PJ
通讯作者：
Mohler PJ
影响因子：
14.9
作者：
Cade L;Reyon D;Hwang WY;Tsai SQ;Patel S;Khayter C;Joung JK;Sander JD;Peterson RT;Yeh JR
通讯作者：
Yeh JR
影响因子：
4.6
作者：
Palpant, Nathan J.;Pabon, Lil;Murry, Charles E.
通讯作者：
Murry, Charles E.