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Vascular system defects and neuronal apoptosis in mice lacking Ras GTPase-activating protein

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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.

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References

  1. Barbacid, M. A. Rev. Biochem. 56, 779–827 (1987).

    Article  CAS  Google Scholar 

  2. Greenwald, I. & Rubin, G. M. Cell 68, 271–281 (1992).

    Article  CAS  PubMed  Google Scholar 

  3. McCormick, F. Curr. Opin. Genet. Dev. 5, 51–55 (1995).

    Article  CAS  PubMed  Google Scholar 

  4. Boguski, M. S. & McCormick, F. Nature 366, 643–654 (1993).

    Article  ADS  CAS  PubMed  Google Scholar 

  5. Rodriguez-Viciana, P. et al. Nature 370, 527–532 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  6. Trahey, M. et al. Science 242, 1697–1700 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Vogel, U. S. et al. Nature 335, 90–93 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Ballester, R. et al. Cell 63, 851–859 (1990).

    Article  CAS  PubMed  Google Scholar 

  9. Martin, G. A. et al. Cell 63, 843–849 (1990).

    Article  CAS  PubMed  Google Scholar 

  10. Xu, G. F. et al. Cell 63, 835–841 (1990).

    Article  CAS  PubMed  Google Scholar 

  11. Maekawa, M. et al. Molec. cell. Biol. 14, 6879–6885 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cullen, P. J. Nature 376, 527–530 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  13. Pawson, T. Nature 373, 573–580 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Molloy, C. J. et al. Nature 342, 711–714 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  15. Anderson, D. et al. Science 250, 979–982 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  16. Ellis, C., Moran, M., McCormick, F. & Pawson, T. Nature 343, 377–381 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Kaplan, D. R., Morrison, D. K., Wong, G., McCormick, F. & Williams, L. T. Cell 61, 125–133 (1990).

    Article  CAS  PubMed  Google Scholar 

  18. Kazlauskas, A., Ellis, C., Pawson, T. & Cooper, J. A. Science 247, 1578–1581 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  19. Moran, M. F., Polakis, P., McCormick, F., Pawson, T. & Ellis, C. Molec. cell. Biol. 11, 1804–1812 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Settleman, J., Narasimhan, V., Foster, L. C. & Weinberg, R. A. Cell 69, 539–549 (1992).

    Article  CAS  PubMed  Google Scholar 

  21. Ridley, A. J. & Hall, A. Cell 70, 389–399 (1992).

    Article  CAS  PubMed  Google Scholar 

  22. Marshall, C. J. Trends Genet. 7, (1991).

  23. Jacks, T. et al. Nature Genet. 7, 353–361 (1994).

    Article  CAS  PubMed  Google Scholar 

  24. Risau, W. in The Development of the Vascular System (eds Feinberg, R. N., Shere, G. K. & Auerbach, R.) 58–68 (Karger, Basel, 1991).

    Google Scholar 

  25. Dumont, D. J. et al. Genes Dev. 8, 1897–1909 (1994).

    Article  CAS  PubMed  Google Scholar 

  26. Henkemeyer, M. et al. Oncogene 9, 1001–1014 (1994).

    CAS  PubMed  Google Scholar 

  27. Gasca, S., Hill, D. P., Klingensmith, J. & Rossant, J. Devl Genet. 17, 141–154 (1995).

    Article  CAS  Google Scholar 

  28. Brannan, C. I. et al. Genes Dev. 8, 1019–1029 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  29. Conlon, R. A., Reaume, A. G. & Rossant, J. Development 121, 1533–1545 (1995).

    CAS  PubMed  Google Scholar 

  30. Fong, G.-H., Rossant, J., Gertsenstien, M. & Breitman, M. L. Nature 376, 66–70 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  31. Shalaby, F. et al. Nature 376, 62–66 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  32. Sato, T. N. et al. Nature 376, 70–74 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  33. Waltenberger, J., Claesson-Welsh, L., Siegbahn, A., Shibuya, M. & Heldin, C.-H. J. biol. Chem. 269, 26988–26995 (1994).

    CAS  PubMed  Google Scholar 

  34. Seetharam, L. et al. Oncogene 10, 135–147 (1995).

    CAS  PubMed  Google Scholar 

  35. Gou, D., Jia, Q., Song, H.-Y., Warren, R. S. & Donner, D. B. J. biol. Chem. 270, 6729–6733 (1995).

    Article  Google Scholar 

  36. Sosnowski, R. G., Feldman, S. & Feramisco, J. R. J. Cell Biol. 121, 113–119 (1993).

    Article  CAS  PubMed  Google Scholar 

  37. Fox, P. L., Sa, G., Dobrowolski, S. F. & Stacey, D. W. Oncogene 9, 3519–3526 (1994).

    CAS  PubMed  Google Scholar 

  38. Nobes, C. D., Hawkins, P., Stephens, L. & Hall, A. J. Cell Sci. 108, 225–233 (1995).

    CAS  PubMed  Google Scholar 

  39. Nobes, C. D. & Hall, A. Cell 81, 53–62 (1995).

    Article  CAS  PubMed  Google Scholar 

  40. Ferrari, G. & Green, L. A. EMBO J. 13, 5922–5928 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Rey, I., Taylor-Harris, P., van Erp, H. & Hall, A. Oncogene 9, 685–692 (1994).

    CAS  PubMed  Google Scholar 

  42. Fernandez-Sarabia, M. J. & Bischoff, J. R. Nature 366, 274–275 (1993).

    Article  ADS  CAS  PubMed  Google Scholar 

  43. Jimenez, B. et al. Oncogene 10, 811–816 (1995).

    CAS  PubMed  Google Scholar 

  44. Tanaka, N. et al. Cell 77, 829–839 (1994).

    Article  CAS  PubMed  Google Scholar 

  45. Wang, H.-G. et al. J. Cell Biol. 129, 1103–1114 (1995).

    Article  CAS  PubMed  Google Scholar 

  46. Tybulewicz, V. L. J., Crawford, C. E., Jackson, P. K., Bronson, R. T. & Mulligan, R. C. Cell 65, 1153–1163 (1991).

    Article  CAS  PubMed  Google Scholar 

  47. Hsieh, C.-L., Vogel, U. S., Dixon, R. A. F. & Francke, U. Somat. Cell molec. Genet. 15, 579–590 (1989).

    Article  CAS  PubMed  Google Scholar 

  48. Wurst, W. & Joyner, A. L. in Gene Targeting: A Practical Approach (ed. Joyner, A. L.) 31–62 (Oxford Univ. Press, 1993).

    Google Scholar 

  49. Nagy, A., Rossant, J., Nagy, R., Abramow-Newerly, W. & Roder, J. C. Proc. natn. Acad. Sci. U.S.A. 90, 8424–8428 (1993).

    Article  ADS  CAS  Google Scholar 

  50. Kim, H. A. et al. Oncogene 11, 325–335 (1995).

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada

    Mark Henkemeyer, Derrick J. Rossi, Douglas P. Holmyard, Mira C. Puri, Geraldine Mbamalu, Kendraprasad Harpal & Tony Pawson

  2. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada

    Derrick J. Rossi, Mira C. Puri & Tony Pawson

  3. Howard Hughes Medical Institute, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    T. Shane Shih & Tyler Jacks

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  1. Mark Henkemeyer
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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

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