Oshima M, Oshima H, Taketo M M
Banyu Tsukuba Research Institute (Merck), Okubo, Japan.
Dev Biol. 1996 Oct 10;179(1):297-302. doi: 10.1006/dbio.1996.0259.
TGF-beta signaling is mediated through two types of serine/threonin kinase-containing receptors, type I (TGF-betaRI) and type II (TGF-betaRII), which form a heteromeric complex. In this signaling complex, ligand binding TGF-betaRII phosphorylates and thereby activates the TGF-betaRI to signal downstream pathways. To determine the role of TGF-betaRII in embryogenesis, we have generated a TGF-betaRII gene (Tgfbr2) knockout mouse line. The heterozygous Tgfbr2 knockout mice are developmentally normal. The homozygous Tgfbr2 mutation causes defects in the yolk sac hematopoiesis and vasculogenesis, resulting in an embryonic lethality around 10.5 days of gestation. This phenotype is indistinguishable from the previously reported embryonic lethality by the homozygous TGF-beta1 gene (Tgfb1) null mutation. In addition, we have generated chimeric mice using a Tgfbr2 (-/-) embryonic stem cell line. Some chimeric mice showed several types of congenital anomalies, suggesting that TGF-beta II is important for normal development in a variety of organs.
转化生长因子-β（TGF-β）信号传导是通过两种含丝氨酸/苏氨酸激酶的受体介导的，即I型（TGF-βRI）和II型（TGF-βRII），它们形成异源复合物。在这个信号复合物中，配体结合TGF-βRII使其磷酸化，从而激活TGF-βRI以向下游信号通路发出信号。为了确定TGF-βRII在胚胎发生中的作用，我们构建了一个TGF-βRII基因（Tgfbr2）敲除小鼠品系。杂合子Tgfbr2敲除小鼠发育正常。纯合子Tgfbr2突变导致卵黄囊造血和血管生成缺陷，导致妊娠约10.5天时胚胎致死。这种表型与先前报道的纯合子转化生长因子-β1基因（Tgfb1）无效突变导致的胚胎致死性无法区分。此外，我们使用Tgfbr2（-/-）胚胎干细胞系构建了嵌合小鼠。一些嵌合小鼠表现出几种类型的先天性异常，表明TGF-β II对多种器官的正常发育很重要。
