Knockout of Wdr1 results in cardiac hypertrophy and impaired cardiac function in adult mouse heart
Knockout of Wdr1 results in cardiac hypertrophy and impaired cardiac function in adult mouse heart
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敲除 Wdr1 会导致成年小鼠心脏肥大和心功能受损
DOI：
10.1016/j.gene.2019.02.023
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发表时间：
2019-05-20
期刊：
影响因子：
3.5
通讯作者：
Yuan, Baiyin
中科院分区：
文献类型：
--
作者：
Huang, Xia;Li, Ziyi;Yuan, Baiyin
WDR1是肌动蛋白解聚因子(ADF)/cofilin的主要辅因子，加速ADF/cofilin介导的肌动蛋白解聚。我们之前已经证明了WDR1介导的肌动蛋白动力学是小鼠出生后心肌生长和成年心肌维持所必需的，其中还没有分析成年心肌细胞特异性Wdrl缺失小鼠的详细表型。在本研究中，我们系统地分析了Wdrl在成年小鼠心脏中的作用。成年心肌细胞特异性Wdrl缺失小鼠(CKO)表现为心肌肥大和心肌纤维化。超声心动图和心电图显示CKO小鼠收缩功能受损，QT间期和T波峰间期延长，T波波幅异常。在CKO小鼠心脏中观察到肌节蛋白、黏附连接蛋白和粘附丝蛋白的水平增加，以及严重的肌动蛋白细丝(F-肌动蛋白)积累。综上所述，这一发现表明WDR1是成年小鼠心脏正常结构和功能的关键因素。
WDR1 is a major cofactor of the actin depolymerizing factor (ADF)/cofilin, accelerating ADF/cofilin-mediated actin disassembly. We had previously showed that WDR1-mediated actin dynamics is required for postnatal myocardial growth and adult myocardial maintenance in mice, in which the detailed phenotypes of adult cardiomyocyte-specific Wdrl deletion mice had not been analyzed. In this study, we systematically analyzed the role of Wdrl in adult mouse heart. Adult cardiomyocyte-specific Wdrl deletion mice (cKO) exhibited cardiac hypertrophy and myocardial fibrosis. Echocardiographic study and electrocardiography revealed impaired contractile function, prolonged QT interval and Tpeak-Tend interval, and abnormal T-wave amplitude in cKO mice. Increased levels of sarcomeric proteins, adherens junction proteins and cofilin, and severe actin filament (F-actin) accumulations were observed in cKO mice heart. Taken together, this finding demonstrates that WDR1 is a critical factor for normal structure and function of adult mouse heart.