Abstract
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. Mutations in the Gap and Nfl 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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Barbacid, M. A. Rev. Biochem. 56, 779–827 (1987).
Greenwald, I. & Rubin, G. M. Cell 68, 271–281 (1992).
McCormick, F. Curr. Opin. Genet. Dev. 5, 51–55 (1995).
Boguski, M. S. & McCormick, F. Nature 366, 643–654 (1993).
Rodriguez-Viciana, P. et al. Nature 370, 527–532 (1994).
Trahey, M. et al. Science 242, 1697–1700 (1988).
Vogel, U. S. et al. Nature 335, 90–93 (1988).
Ballester, R. et al. Cell 63, 851–859 (1990).
Martin, G. A. et al. Cell 63, 843–849 (1990).
Xu, G. F. et al. Cell 63, 835–841 (1990).
Maekawa, M. et al. Molec. cell. Biol. 14, 6879–6885 (1994).
Cullen, P. J. Nature 376, 527–530 (1995).
Pawson, T. Nature 373, 573–580 (1995).
Molloy, C. J. et al. Nature 342, 711–714 (1989).
Anderson, D. et al. Science 250, 979–982 (1990).
Ellis, C., Moran, M., McCormick, F. & Pawson, T. Nature 343, 377–381 (1990).
Kaplan, D. R., Morrison, D. K., Wong, G., McCormick, F. & Williams, L. T. Cell 61, 125–133 (1990).
Kazlauskas, A., Ellis, C., Pawson, T. & Cooper, J. A. Science 247, 1578–1581 (1990).
Moran, M. F., Polakis, P., McCormick, F., Pawson, T. & Ellis, C. Molec. cell. Biol. 11, 1804–1812 (1991).
Settleman, J., Narasimhan, V., Foster, L. C. & Weinberg, R. A. Cell 69, 539–549 (1992).
Ridley, A. J. & Hall, A. Cell 70, 389–399 (1992).
Marshall, C. J. Trends Genet. 7, (1991).
Jacks, T. et al. Nature Genet. 7, 353–361 (1994).
Risau, W. in The Development of the Vascular System (eds Feinberg, R. N., Shere, G. K. & Auerbach, R.) 58–68 (Karger, Basel, 1991).
Dumont, D. J. et al. Genes Dev. 8, 1897–1909 (1994).
Henkemeyer, M. et al. Oncogene 9, 1001–1014 (1994).
Gasca, S., Hill, D. P., Klingensmith, J. & Rossant, J. Devl Genet. 17, 141–154 (1995).
Brannan, C. I. et al. Genes Dev. 8, 1019–1029 (1994).
Conlon, R. A., Reaume, A. G. & Rossant, J. Development 121, 1533–1545 (1995).
Fong, G.-H., Rossant, J., Gertsenstien, M. & Breitman, M. L. Nature 376, 66–70 (1995).
Shalaby, F. et al. Nature 376, 62–66 (1995).
Sato, T. N. et al. Nature 376, 70–74 (1995).
Waltenberger, J., Claesson-Welsh, L., Siegbahn, A., Shibuya, M. & Heldin, C.-H. J. biol. Chem. 269, 26988–26995 (1994).
Seetharam, L. et al. Oncogene 10, 135–147 (1995).
Gou, D., Jia, Q., Song, H.-Y., Warren, R. S. & Donner, D. B. J. biol. Chem. 270, 6729–6733 (1995).
Sosnowski, R. G., Feldman, S. & Feramisco, J. R. J. Cell Biol. 121, 113–119 (1993).
Fox, P. L., Sa, G., Dobrowolski, S. F. & Stacey, D. W. Oncogene 9, 3519–3526 (1994).
Nobes, C. D., Hawkins, P., Stephens, L. & Hall, A. J. Cell Sci. 108, 225–233 (1995).
Nobes, C. D. & Hall, A. Cell 81, 53–62 (1995).
Ferrari, G. & Green, L. A. EMBO J. 13, 5922–5928 (1994).
Rey, I., Taylor-Harris, P., van Erp, H. & Hall, A. Oncogene 9, 685–692 (1994).
Fernandez-Sarabia, M. J. & Bischoff, J. R. Nature 366, 274–275 (1993).
Jimenez, B. et al. Oncogene 10, 811–816 (1995).
Tanaka, N. et al. Cell 77, 829–839 (1994).
Wang, H.-G. et al. J. Cell Biol. 129, 1103–1114 (1995).
Tybulewicz, V. L. J., Crawford, C. E., Jackson, P. K., Bronson, R. T. & Mulligan, R. C. Cell 65, 1153–1163 (1991).
Hsieh, C.-L., Vogel, U. S., Dixon, R. A. F. & Francke, U. Somat. Cell molec. Genet. 15, 579–590 (1989).
Wurst, W. & Joyner, A. L. in Gene Targeting: A Practical Approach (ed. Joyner, A. L.) 31–62 (Oxford Univ. Press, 1993).
Nagy, A., Rossant, J., Nagy, R., Abramow-Newerly, W. & Roder, J. C. Proc. natn. Acad. Sci. U.S.A. 90, 8424–8428 (1993).
Kim, H. A. et al. Oncogene 11, 325–335 (1995).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Henkemeyer, M., Rossi, D., Holmyard, D. et al. Vascular system defects and neuronal apoptosis in mice lacking Ras GTPase-activating protein. Nature 377, 695–701 (1995). https://doi.org/10.1038/377695a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/377695a0
This article is cited by
-
Genetics of brain arteriovenous malformations and cerebral cavernous malformations
Journal of Human Genetics (2023)
-
Temporospatial inhibition of Erk signaling is required for lymphatic valve formation
Signal Transduction and Targeted Therapy (2023)
-
The therapeutic potential of neurofibromin signaling pathways and binding partners
Communications Biology (2023)
-
Molecular and genetic mechanisms in brain arteriovenous malformations: new insights and future perspectives
Neurosurgical Review (2022)
-
Vascular endothelial cell specification in health and disease
Angiogenesis (2021)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
