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首页> 外文期刊>Molecular and Cellular Biology >PINCH1 Plays an Essential Role in Early Murine Embryonic Development but Is Dispensable in Ventricular Cardiomyocytes
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PINCH1 Plays an Essential Role in Early Murine Embryonic Development but Is Dispensable in Ventricular Cardiomyocytes

机译:PINCH1在早期小鼠胚胎发育中起重要作用,但在心室心肌细胞中可有可无

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PINCH1, an adaptor protein composed of five LIM domains, mediates protein-protein interactions and functions as a component of the integrin-integrin-linked kinase (ILK) complex. The integrin-ILK signaling complex plays a pivotal role in cell motility, proliferation, and survival during embryonic development of many animal species. To elucidate the physiological function of PINCH1 in mouse embryonic development, we have deleted the mouse PINCH1 gene by homologous recombination. Mice heterozygous for PINCH1 are viable and indistinguishable from wild-type littermates. However, no viable homozygous offspring were observed from PINCH1+/? intercrosses. Histological analysis of homozygous mutant embryos revealed that they had a disorganized egg cylinder by E5.5, which degenerated by E6.5. Furthermore, E5.5 PINCH1?/? embryos exhibited decreased cell proliferation and excessive cell death. We have also generated and analyzed mice in which PINCH1 has been specifically deleted in ventricular cardiomyocytes. These mice exhibit no basal phenotype, with respect to mouse survival, cardiac histology, or cardiac function as measured by echocardiography. Altogether, these data indicate that PINCH1 plays an essential role in early murine embryonic development but is dispensable in ventricular cardiomyocytes.
机译:PINCH1是由五个LIM域组成的衔接蛋白,介导蛋白质与蛋白质的相互作用,并起整合素-整合素连接的激酶(ILK)复合体的作用。整联蛋白-ILK信号复合物在许多动物胚胎发育过程中的细胞运动,增殖和存活中起关键作用。为了阐明PINCH1在小鼠胚胎发育中的生理功能,我们通过同源重组删除了小鼠 PINCH1 基因。 PINCH1 杂合的小鼠与野生型同窝仔动物是可行的并且没有区别。但是,在 PINCH1 + / 杂交中没有观察到纯合子代。对纯合突变体胚胎的组织学分析表明,通过E5.5,它们具有混乱的卵筒,并通过E6.5变性。此外,E5.5 PINCH1 / 胚胎显示出减少的细胞增殖和过度的细胞死亡。我们还生成并分析了其中 PINCH1 在心室心肌细胞中特异性缺失的小鼠。这些小鼠在通过超声心动图测量的小鼠存活率,心脏组织学或心脏功能方面无基础表型。总而言之,这些数据表明PINCH1在早期鼠胚胎发育中起着重要作用,但在心室心肌细胞中是不可缺少的。

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