Targeted Genomic Disruption of H-ras and N-ras, Individually or in Combination, Reveals the Dispensability of Both Loci for Mouse Growth and Development

• DOI: 10.1128/mcb.21.5.1444-1452.2001
• Publication Date: 2002-07-27T10:03:53Z
• Authors: Luis M. Esteban; Carlos Vicario-Ab...; Pedro Fernández-S...; Alberto Fernández...; Nalini Swaminathan; Kate Yienger; Eva Lopez; Marcos Malumbres; Ron McKay; Jerrold M. Ward; Angel Pellicer; Eugenio Santos
• Keywords: Null allele; Knockout mouse; Gene knockout; Conditional gene knockout; Gene targeting; Wild type

Mammalian cells harbor three highly homologous and widely expressed members of the ras family (H-ras, N-ras, K-ras), but it remains unclear whether they play specific or overlapping cellular roles. To gain insight into such functional roles, here we generated analyzed H-ras null mutant mice, which were then also bred with N-ras knockout animals to ascertain viability properties potential double mutations in both loci. Mating among heterozygous H-ras(+/-) mice produced H-ras(-/-) offspring a normal Mendelian pattern inheritance, indicating that loss did not interfere embryonic fetal uterus. Homozygous reached sexual maturity at same age as their littermates, males females fertile. Characterization lymphocyte subsets spleen thymus showed no significant differences between wild-type mice. Analysis neuronal markers brains disruption this locus impair alter development. Breeding our previously available mutants gave rise viable (H-ras(-/-)/N-ras(-/-)) expressing only K-ras genes grew normally, fertile, show any obvious phenotype. Interestingly, however, lower-than-expected numbers adult, consistently obtained crosses N-ras/H-ras Our results indicate that, for gene function is dispensable mouse development, growth, fertility, Additionally, genes, appears be essential sufficient