权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Functional redundancy of the three ras genes which uses ras genes knock-out mice.

三个ras基因的功能冗余采用ras基因敲除小鼠。

基本信息

批准号：
10670193
负责人：
NAKAMURA Kenji
金额：
$ 2.05万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670193/
关键词：
K-ras H-ras N-ras gene replacement ES cells gene targeting knock-out mice mouse

项目摘要

In mammals, three ras genes, H-ras, N-ras and K-ras encode homologous but distinct 21-kDa Ras proteins. No clear evidence for the individual in vivo functions of each ras gene and functional redundancy of the three ras genes has yet been reported. We herein show the functional redundancy of the three ras genes, H-ras, N-ras and K-ras, by investigating the phenotypes of mice deficient in each of these genes, mice deficient in multiple ras genes and H-ras transgenic mice. H-ras-/- mice and N-ras-/- mice as well as a substantial proportion of H-ras-/- N-ras-/- mice that express only the K-ras gene are viable, while K-ras-/- mice have been previously shown to be embryonically lethal. An investigation of neonatal death of N-ras-/- K-ras+/- and H-ras-/- N-ras-/- mice has shown that a part of these mice died because of chylous ascites and intestinal lymphedema. Most ras mutant mice lacking 2 or more ras alleles exhibited a similar phenotype. The incidence of intestinal lymphedema increases as the number of null alleles of any three ras genes increase, which thus suggests that the function of three ras genes is redundant. To prove this hypothesis, we introduce the human H-ras transgenes into single and multiple ras mutant mice and found the H-ras transgenes to rescue all abnormalities exhibited in the development of these ras mutant mice. We therefore conclude that the function of the ras genes is redundant in vivo.

在哺乳动物中，三个ras基因，H-ras， N-ras和K-ras编码同源但不同的21-kDa ras蛋白。目前还没有明确的证据表明每个ras基因的个体体内功能和三个ras基因的功能冗余。本文通过研究缺乏H-ras、N-ras和K-ras这三个ras基因的小鼠、缺乏多个ras基因的小鼠和H-ras转基因小鼠的表型，证明了它们的功能冗余性。H-ras-/-小鼠和N-ras-/-小鼠以及大量只表达K-ras基因的H-ras-/- N-ras-/-小鼠是存活的，而K-ras-/-小鼠先前已被证明是胚胎致死的。一项对N-ras-/- K-ras+/-和H-ras-/- N-ras-/-小鼠新生儿死亡的调查显示，这些小鼠的部分死亡原因是乳糜腹水和肠淋巴水肿。大多数缺乏2个或更多ras等位基因的ras突变小鼠表现出相似的表型。肠道淋巴水肿的发生率随着任意三个ras基因的零等位基因数量的增加而增加，这表明三个ras基因的功能是冗余的。为了证明这一假设，我们将人类H-ras转基因引入到单个和多个ras突变小鼠中，发现H-ras转基因可以挽救这些ras突变小鼠发育过程中表现出的所有异常。因此我们得出结论，ras基因的功能在体内是冗余的。