...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >pak2a mutations cause cerebral hemorrhage in redhead zebrafish
【24h】

pak2a mutations cause cerebral hemorrhage in redhead zebrafish

机译：pak2a突变导致红发斑马鱼脑出血

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The zebrafish is a powerful model for studying vascular development, demonstrating remarkable conservation of this process with mammals. Here, we identify a zebrafish mutant, redhead (rhd~(m/149)), that exhibits embryonic CNS hemorrhage with intact gross development of the vasculature and normal hemostatic function. We show that the rhd phenotype is caused by a hypo-morphic mutation in p21-activated kinase 2a (pak2a). PAK2 is a kinase that acts downstream of the Rho-family GTPases CDC42 and RAC and has been implicated in angiogenesis, regulation of cy-toskeletal structure, and endothelial cell migration and contractility among other functions. Correction of the Pak2a-deficient phenotype by Pak2a overexpression depends on kinase activity, implicating Pak2 signaling in the maintenance of vascular integrity. Rescue by an endothelial-specific transgene further suggests that the hemorrhage seen in Pak2a deficiency is the result of an autonomous endothelial cell defect. Reduced expression of another PAK2 ortholog, pak2b, in Pak2a-deficient embryos results in a more severe hemorrhagic phenotype, consistent with partially overlapping functions for these two orthologs. These data provide in vivo evidence for a critical function of Pak2 in vascular integrity and demonstrate a severe disease phenotype resulting from loss of Pak2 function.
机译：斑马鱼是研究血管发育的有力模型，证明了哺乳动物对这一过程的出色保护。在这里，我们确定了斑马鱼突变体，红发（rhd〜（m / 149）），表现出胚胎中枢神经系统出血与完整的脉管系统的全面发展和正常的止血功能。我们表明rhd表型是由p21激活的激酶2a（pak2a）中的一个亚型突变引起的。 PAK2是一种在Rho家族GTPases CDC42和RAC下游起作用的激酶，与血管生成，细胞骨架结构的调节以及内皮细胞的迁移和收缩等功能有关。 Pak2a过表达对Pak2a缺陷表型的校正取决于激酶活性，在维持血管完整性方面牵涉Pak2信号传导。内皮特异性转基因的抢救进一步表明，Pak2a缺乏症中的出血是自主性内皮细胞缺陷的结果。 Pak2a缺陷型胚胎中另一种PAK2直系同源物pak2b的表达降低导致更严重的出血表型，与这两个直系同源物的部分重叠功能一致。这些数据提供了Pak2在血管完整性中的关键功能的体内证据，并证明了Pak2功能丧失导致的严重疾病表型。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号