Vascular system defects and neuronal apoptosis in mice lacking ras GTPase-activating protein
Henkemeyer, M.; Rossi, D.J.; Holmyard, D.P.; Puri, M.C.; Mbamalu, G.; Harpal, K.; Shih, T.S.; Jacks, T.; Pawson, T.
Nature 377(6551): 695-701
The gene encoding p120-rasGAP, a negative regulator of Ras, has been disrupted in mice. This Gap mutation affects the ability of endothelial cells to organize into a highly vascularized network and results in extensive neuronal cell death. Mutati ons in the Gap and Nf1 genes have a synergistic effect, such that embryos homozygous for mutations in both genes show an exacerbated Gap phenotype. Thus rasGAP and neurofibromin act together to regulate Ras activity during embryonic development.