Ras-guanine nucleotide exchange factor Sos2 is dispensable for mouse growth and development

The mammalian sos1 and sos2 genes encode highly homologous members of the S on of-sevenless family of guanine nucleotide exchange factors. They are ubi quitously expressed and play key roles in transmission of signals initiated by surface protein tyrosine kinases that are transduced into the cell thro ugh the action of membrane-associated Ras proteins. Recent reports showed t hat targeted disruption of the sos1 locus results in embryonic lethality. T o gain insight into the in vivo function of sos2, we disrupted its catalyti c CDC25-H domain by means of gene targeting techniques. Mating among hetero zygous sos2(+/-) mice produced viable sos2(-/-) offspring with a normal Men delian pattern of inheritance, indicating that the loss of sos2 does not in terfere with embryo viability in the uterus. Adult homozygous mutant sos2(- /-) mice reached sexual maturity at the same age as their wild-type litterm ates, and bath male and female null mutants were fertile. Histopathological analysis showed no observable differences between mutant and wild-type mic e. Our results show that unlike the case for sos1, sos2 gene function is di spensable for normal mouse development, growth, and fertility.