Rheb Is Essential for Murine Development
Rheb Is Essential for Murine Development
复制标题
DOI：
10.1128/mcb.00985-10
复制
发表时间：
2011-04-01
影响因子：
5.3
通讯作者：
Elgersma, Ype
中科院分区：
文献类型：
--
作者：
Goorden, Susanna M. I.;Hoogeveen-Westerveld, Marianne;Elgersma, Ype
大脑中富集的 Ras 同源物 (Rheb) 将生长因子信号传导与雷帕霉素复合物 1 (TORC1) 靶点的激活结合起来。为了研究它在哺乳动物中的作用，我们培育了一只 Rheb 基因敲除小鼠。与 mTOR 或 mTOR (Raptor) 突变体的调节相关蛋白相反，Rheb(-/-) 胚胎的内细胞团正常分化。然而，Rheb(-/-) 胚胎在妊娠中期左右死亡，很可能是由于心血管系统发育受损。 Rheb(-/-)胚胎成纤维细胞显示TORC1活性降低、变小并且增殖受损。 Rheb杂合性延长了结节性硬化症复合体1缺陷（Tsc1（-/-））胚胎的寿命，表明小鼠中Tsc1和Rheb基因之间存在遗传相互作用。
Ras homolog enriched in brain (Rheb) couples growth factor signaling to activation of the target of rapamycin complex 1 (TORC1). To study its role in mammals, we generated a Rheb knockout mouse. In contrast to mTOR or regulatory-associated protein of mTOR (Raptor) mutants, the inner cell mass of Rheb(-/-) embryos differentiated normally. Nevertheless, Rheb(-/-) embryos died around midgestation, most likely due to impaired development of the cardiovascular system. Rheb(-/-) embryonic fibroblasts showed decreased TORC1 activity, were smaller, and showed impaired proliferation. Rheb heterozygosity extended the life span of tuberous sclerosis complex 1-deficient (Tsc1(-/-)) embryos, indicating that there is a genetic interaction between the Tsc1 and Rheb genes in mouse.