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Combinatorial genetic replenishments in myocardial and outflow tract tissues restore heart function in tnnt2 mutant zebrafish 期刊论文

编号：

F189B93DBDB65BE5798C909BE4B250C2
作者：

Liu, Lian^[1];Fei, Fei^[2,3];Zhang, Ranran^[4];Wu, Fang^[1];Yang, Qian^[1];Wang, Feng^[1];Sun, Shaoyang(孙少阳)^[3]Zhao, Hui^[5];Li, Qiang^[6];Wang, Lei^[3];Wang, Youhua^[5];Gui, Yonghao(桂永浩)*^[1]Wang, Xu(王旭)*^[2,3]
语种：

英文
期刊：

BIOLOGY OPEN ISSN：2046-6390 2019 年 8 卷 12 期 ; DEC
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关键词：

Zebrafish Cardiac troponin T (TNNT2) Conditional transgene Genetic replenishment Dilated cardiomyopathy (DCM) Outflow tract (OFT) Cardiomyocyte
摘要：

Cardiac muscle troponin T (Tnnt2) mediates muscle contraction in response to calcium ion dynamics, and Tnnt2 mutations are associated with multiple types of cardiomyopathy. Here, we employed a zebrafish model to investigate the genetic replenishment strategies of using conditional and inducible promoters to rescue the deficiencies in the heart. tnnt2a mutations were induced in zebrafish via the CRISPR/Cas9 technique, and the mutants displayed heart arrest and dilated cardiomyopathy-like phenotypes. We first utilized the classic myocardial promoter of the myl7 and TetOn inducible system to restore tnnt2a expression in myocardial tissue in tnnt2a mutant zebrafish. However, this attempt failed to recover normal heart function and circulation, although heart pumping was partially restored. Further analyses via both RNA-seq and immunofluorescence indicated that Tnnt2a, which was also expressed in a novel group of myl7-negative smooth muscle cells on the outflow tract (OFT), was indispensably responsible for the normal mechanical dynamics of OFT. Lastly, tnnt2 expression induced by OFT cells in addition to the myocardial cells successfully rescued heart function and circulation in tnnt2a mutant zebrafish. Together, our results reveal the significance of OFT expression of Tnnt2 for cardiac function and demonstrate zebrafish larva as a powerful and convenient in vivo platform for studying cardiomyopathy and the relevant therapeutic strategies.
推荐引用方式
GB/T 7714：

Liu Lian,Fei Fei,Zhang Ranran, et al. Combinatorial genetic replenishments in myocardial and outflow tract tissues restore heart function in tnnt2 mutant zebrafish [J].BIOLOGY OPEN,2019,8(12).
APA：

Liu Lian,Fei Fei,Zhang Ranran,Wu Fang,&Wang Xu.(2019).Combinatorial genetic replenishments in myocardial and outflow tract tissues restore heart function in tnnt2 mutant zebrafish .BIOLOGY OPEN,8(12).
MLA：

Liu Lian, et al. "Combinatorial genetic replenishments in myocardial and outflow tract tissues restore heart function in tnnt2 mutant zebrafish" .BIOLOGY OPEN 8,12(2019).
入库时间：

2020/4/12 3:15:05
更新时间：

2020/4/12 3:15:05

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