Umanoff H, Edelmann W, Pellicer A, Kucherlapati R
Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461.
Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1709-13. doi: 10.1073/pnas.92.5.1709.
The mammalian ras gene family encodes key cell-signaling, cell growth-related proteins that have been highly conserved in species from yeast to man. Specific point mutations in the ras genes are associated with various mammalian tumors. To understand the developmental role of the N-ras protooncogene in the mouse, we have disrupted its gene function by homologous recombination in embryonic stem cells. Mice derived from these cells that are homozygous for the N-ras mutation do not produce any detectable N-Ras protein and are morphologically and histologically indistinguishable from their heterozygous and wild-type siblings. Since N-ras is expressed at high levels in hematopoietic cells, we examined different populations of cells in peripheral blood and found no differences between mutant and normal animals. Our results show that N-ras gene function is dispensable for normal mouse development, growth, and fertility.
哺乳动物的ras基因家族编码关键的细胞信号传导、细胞生长相关蛋白,这些蛋白在从酵母到人类的物种中高度保守。ras基因中的特定点突变与各种哺乳动物肿瘤相关。为了了解N-ras原癌基因在小鼠发育中的作用,我们通过胚胎干细胞中的同源重组破坏了其基因功能。由这些细胞衍生而来的、N-ras突变纯合的小鼠不产生任何可检测到的N-Ras蛋白,在形态和组织学上与它们的杂合和野生型同胞没有区别。由于N-ras在造血细胞中高水平表达,我们检查了外周血中的不同细胞群体,发现突变动物和正常动物之间没有差异。我们的结果表明,N-ras基因功能对于正常小鼠的发育、生长和生育能力是可有可无的。