p53-dependent apoptosis produced by Rb-deficiency in the developing mouse lens (original) (raw)

Nature volume 371, pages 72–74 (1994)Cite this article

Abstract

THE retinoblastoma tumour-suppressor gene (RB) has been implicated in negative growth regulation, induction of differentiation, and inhibition of cellular transformation1. Homozygous inactivation of the Rb gene in the mouse leads to mid-gestational lethality with defects in erythropoiesis and neurogenesis2–4. Here we describe the effects of the _Rb_-deficient state on the development of the ocular lens. The regional compartmentalization of growth, differentiation and apoptosis in the developing lens provides an ideal system to examine more closely the relationships of these processes in vivo. We demonstrate that loss of Rb function is associated with unchecked proliferation, impaired expression of differentiation markers, and inappropriate apoptosis in lens fibre cells. In addition, we show that ectopic apoptosis in _Rb_-deficient lenses is dependent on p53, because embryos doubly null for Rb and p53 show a nearly complete suppression of this effect. This developmental system provides a framework for understanding the consequences of the frequent mutation of both RB and p53 in human cancer.

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References

  1. Hollingsworth, R. E., Hensey, C. E. & Lee, W. H. Curr. Opin. Genet. Dev. 3, 55–62 (1993).
    Article CAS Google Scholar
  2. Lee, E. Y.-H. P. et al. Nature 359, 288–294 (1992).
    Article ADS CAS Google Scholar
  3. Jacks, T. et al. Nature 359, 295–300 (1992).
    Article ADS CAS Google Scholar
  4. Clarke, A. R. et al. Nature 359, 328–330 (1992).
    Article ADS CAS Google Scholar
  5. Pei, Y. F. & Rhodin, J. A. G. Anat. Rec. 168, 105–126 (1970).
    Article CAS Google Scholar
  6. Silver, J. & Hughes, A. F. W. J. Morphol. 140, 159–170 (1973).
    Article CAS Google Scholar
  7. Ishazaki, Y., Voyvodic, J. T., Burne, J. F. & Raff, M. C. J. Cell Biol. 121, 899–908 (1993).
    Article Google Scholar
  8. McAvoy, J. W. J. Embryol. exp. Morph. 44, 149–165 (1978).
    CAS PubMed Google Scholar
  9. Shiels, A., Griffin, C. S. & Muggleton-Harris, A. L. Biochim. biophys. Acta 1097, 318–324 (1991).
    Article CAS Google Scholar
  10. Yancey, S. B., Koh, K., Chung, J. & Revel, J. P. J. Cell Biol. 106, 705–714 (1988).
    Article CAS Google Scholar
  11. Gavrieli, Y., Sherman, Y. & BenSasson, S. A. J. Cell Biol. 119, 493–501 (1992).
    Article CAS Google Scholar
  12. Yonish-Rouach, E. et al. Nature 352, 345–347 (1991).
    Article ADS CAS Google Scholar
  13. Shaw, P. et al. Proc. natn. Acad. Sci. U.S.A. 89, 4495–4499 (1992).
    Article ADS CAS Google Scholar
  14. Debbas, M. & White, E. Genes Dev. 7, 546–554 (1993).
    Article CAS Google Scholar
  15. Lowe, S. W., Jacks, T., Housman, D. E. & Ruley, H. E. Proc. natn. Acad. Sci. U.S.A. 91, 2026–2030 (1994).
    Article ADS CAS Google Scholar
  16. Lowe, S. W. et al. Nature 362, 847–849 (1993).
    Article ADS CAS Google Scholar
  17. Clarke, A. R. et al. Nature 362, 849–852 (1993).
    Article ADS CAS Google Scholar
  18. Berges, R. R. et al. Proc. natn. Acad. Sci. U.S.A. 90, 8910–8914 (1993).
    Article ADS CAS Google Scholar
  19. Williams, B. O. et al. Nature Genet. 7, 480–484 (1994).
    Article CAS Google Scholar
  20. Whyte, P. et al. Nature 334, 124–129 (1988).
    Article ADS CAS Google Scholar
  21. Pines, J. & Hunter, T. Nature 346, 760–763 (1990).
    Article ADS CAS Google Scholar
  22. Williams, B. O. et al. EMBO J. (in the press).
  23. Hawley-Nelson, P. et al. EMBO J. 8, 3905–3910 (1989).
    Article CAS Google Scholar
  24. Watanabe, S., Kanda, T. & Yoshiike, K. J. Virol. 63, 965–969 (1989).
    CAS PubMed PubMed Central Google Scholar
  25. Munger, K. et al. J. Virol. 63, 4417–4421 (1989).
    CAS PubMed PubMed Central Google Scholar
  26. Mahon, K. et al. Science 235, 1622–1628 (1987).
    Article ADS CAS Google Scholar
  27. Griep, A. et al. J. Virol. 67, 1373–1384 (1993).
    CAS PubMed PubMed Central Google Scholar
  28. Pan, H. & Griep, A. E. Genes Dev. 8, 1285–1299 (1994).
    Article CAS Google Scholar

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, 10461, USA
    Sharon D. Morgenbesser & Ronald A. DePinho
  2. Howard Hughes Medical Institute, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA
    Bart O. Williams & Tyler Jacks

Authors

  1. Sharon D. Morgenbesser
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  2. Bart O. Williams
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  3. Tyler Jacks
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  4. Ronald A. DePinho
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Morgenbesser, S., Williams, B., Jacks, T. et al. _p53_-dependent apoptosis produced by _Rb_-deficiency in the developing mouse lens.Nature 371, 72–74 (1994). https://doi.org/10.1038/371072a0

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