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Accentuated apoptosis in normally developing p53 knockout mouse embryos following genotoxic stress

Oncogene volume 18, pages 2901–2907 (1999)Cite this article

Abstract

In order to identify the alternative pathways which may substitute for the p53 function during embryogenesis, we have focused our studies on p53−/− normally developing mouse embryos that survived a genotoxic stress. We assumed that under these conditions p53-independent pathways, which physiologically control genomic stability, are enhanced. We found that while p53+/+ mouse embryos elicited, as expected, a p53-dependent apoptosis, p53−/− normally developing mice exhibited an accentuated p53-independent apoptotic response. The p53-dependent apoptosis detected in p53+/+ embryos, was an immediate reaction mostly detected in the brain, whereas the p53-independent apoptosis was a delayed reaction with a prominent pattern observed in epithelial cells of most organs in the p53-deficient mice only. These results suggest that in the absence of p53-dependent apoptosis, which is a fast response to damaged DNA, p53-independent apoptotic pathways, with slower kinetics, are turned on to secure genome stability.

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Acknowledgements

The authors wish to thank Professor Ben-Zion Shilo of Department of Molecular Genetics; David Wiseman of the Department of Molecular Biology of the Weizmann Institute for fruitful discussion and criticism and Ms Hassida Orenstein for excellent technical assistance. Ms Vivienne Laufer helped in the manuscript preparation. This work was supported in part by grants from the Leo and Julia Forchheimer Center for Molecular Genetics, the Min-erva Foundation and BSF. Varda Rotter is the incumbent of the Norman and Helen Asher Professorial Chair in Cancer Research at the Weizmann Institute.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Assaf Harofe, Medical Center, Tel Aviv University, Tel Aviv, Israel

    Jene Frenkel & Dan Sherman

  2. Department of Embryology and Teratology, Sackler School of Medicine Tel Aviv University, Tel Aviv, Israel

    Amos Fein

  3. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel

    Jene Frenkel, Dov Schwartz, Nava Almog, Ahuva Kapon, Naomi Goldfinger & Varda Rotter

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  1. Jene Frenkel
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Frenkel, J., Sherman, D., Fein, A. et al. Accentuated apoptosis in normally developing p53 knockout mouse embryos following genotoxic stress. Oncogene 18, 2901–2907 (1999). https://doi.org/10.1038/sj.onc.1202518

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