Partial functional overlap of the three ras genes in mouse embryonic development
Partial functional overlap of the three ras genes in mouse embryonic development
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DOI：
10.1038/sj.onc.1210956
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发表时间：
2008-05-08
期刊：
影响因子：
8
通讯作者：
Katsuki, M.
中科院分区：
文献类型：
--
作者：
Nakamura, K.;Ichise, H.;Katsuki, M.
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。我们通过研究一个或多个ras基因缺陷小鼠的表型，研究了这三个ras基因在小鼠胚胎发育中的体内功能关系。H-ras(-/-)小鼠和N-ras(-/-)小鼠以及相当一部分只表达K-ras基因的H-ras(-/-)/N-ras(-/-)小鼠是存活的，而K-ras(-/-)小鼠是胚胎致死的，正如先前报道的那样。N-ras(-/-)/K-ras(+/-)小鼠新生儿死亡，而H-ras(-/-)/K-ras(-/-)胚胎死亡明显早于K-ras纯合子突变胎儿。为了进一步研究ras基因在胚胎发育中的功能关系，我们将人H-ras基因导入单个或多个ras突变小鼠中，发现转基因小鼠，包括三个ras突变小鼠，在纠正K-ras缺失突变小鼠的心脏薄壁的同时，使胚胎免于死亡。原位杂交结果表明，在胚胎E13.5和E15.5天，转基因H-ras基因在心脏等主要器官中的表达强度高于内源ras基因。因此，我们得出结论，ras基因在小鼠胚胎发育中的功能部分重叠。
In mammals, three ras genes, H-ras, N-ras and K-ras, encode homologous but distinct 21-kDa Ras proteins. We examined the in vivo functional relationship of the three ras genes in mouse embryonic development by investigating the phenotypes of mice deficient in one or multiple ras genes. H-ras(-/-) mice and N-ras(-/-) mice as well as a substantial proportion of H-ras(-/-)/N-ras(-/-) mice expressing only the K-ras gene were viable, while K-ras(-/-) mice were embryonically lethal, as have been reported previously. N-ras(-/-)/K-ras(+/-) mice died neonatally, while H-ras(-/-)/K-ras(-/-) embryos died much earlier than K-ras homozygous mutant fetuses. To further investigate the functional relationship of the ras genes in embryonic development, we introduced a human H-ras transgene into single or multiple ras mutant mice and found that the transgene rescued mice, including triple ras mutants, from embryonic lethality in association with correction of thin ventricular walls of the heart in null K-ras mutant mice. In situ hybridization revealed that the expression of the H-ras transgene on embryonic day E13.5 and E15.5 was more intense in major organs, including the heart, than those of endogenous ras genes. We therefore conclude that the functions of the ras genes are partially overlapping in mouse embryonic development.