Sato T N, Tozawa Y, Deutsch U, Wolburg-Buchholz K, Fujiwara Y, Gendron-Maguire M, Gridley T, Wolburg H, Risau W, Qin Y
Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110, USA.
Nature. 1995 Jul 6;376(6535):70-4. doi: 10.1038/376070a0.
Tie-1 and Tie-2 define a new class of receptor tyrosine kinases that are specifically expressed in developing vascular endothelial cells. To study the functions of Tie-1 and Tie-2 during vascular endothelial cell growth and differentiation in vivo, targeted mutations of the genes in mice were introduced by homologous recombination. Embryos deficient in Tie-1 failed to establish structural integrity of vascular endothelial cells, resulting in oedema and subsequently localized haemorrhage. However, analyses of embryos deficient in Tie-2 showed that it is important in angiogenesis, particularly for vascular network formation in endothelial cells. This result contrasts with previous reports on Tie-2 function in vasculogenesis and/or endothelial cell survival. Our in vivo analyses indicate that the structurally related receptor tyrosine kinases Tie-1 and Tie-2 have important but distinct roles in the formation of blood vessels.
Tie-1和Tie-2定义了一类新的受体酪氨酸激酶，它们在发育中的血管内皮细胞中特异性表达。为了研究Tie-1和Tie-2在体内血管内皮细胞生长和分化过程中的功能，通过同源重组在小鼠中引入了基因的靶向突变。缺乏Tie-1的胚胎未能建立血管内皮细胞的结构完整性，导致水肿并随后局部出血。然而，对缺乏Tie-2的胚胎的分析表明，它在血管生成中很重要，特别是对于内皮细胞中的血管网络形成。这一结果与先前关于Tie-2在血管发生和/或内皮细胞存活中的功能的报道形成对比。我们的体内分析表明，结构相关的受体酪氨酸激酶Tie-1和Tie-2在血管形成中具有重要但不同的作用。
