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Partial functional overlap of the three ras genes in mouse embryonic development

机译：小鼠胚胎发育中三个ras基因的部分功能重叠

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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.
机译：在哺乳动物中，三个ras基因H-ras，N-ras和K-ras编码同源但截然不同的21-kDa Ras蛋白。我们通过调查缺乏一种或多种ras基因的小鼠的表型，检查了三种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？/？小鼠以及相当大比例的H-ras？/？/ N-ras？/？只表达K-ras基因的小鼠是有生存力的，而K-rasα/β则是可行的。如先前所报道，小鼠在胚胎上具有致死性。 N-ras？/？/ K-ras + /？小鼠新生儿死亡，而H-ras？/？/ K-ras？/？胚胎比K-ras纯合突变胎儿更早死亡。为了进一步研究ras基因在胚胎发育中的功能关系，我们将人类H-ras转基因引入单个或多个ras突变小鼠中，发现该转基因从胚胎致死力中拯救了小鼠，包括三重ras突变体，并纠正了空K-ras突变小鼠中心脏的薄心室壁。原位杂交显示，H-ras转基因在胚胎第E13.5和E15.5日的表达在包括心脏在内的主要器官中均比内源ras基因的表达更为强烈。因此，我们得出结论，ras基因的功能在小鼠胚胎发育中部分重叠。

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