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Testicular wild-type p53 expression in transgenic mice induces spermiogenesis alterations ranging from differentiation defects to apoptosis

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Abstract

While p53 is dispensable for development, an excess of p53 has dramatic consequences on the embryogenesis and on the cell differentiation. In an attempt to analyse in vivo the effects of p53 activity, we have generated transgenic mice expressing the wild-type p53 under the control of the metallothionein I promoter. In the three transgenic lines established, exogenous p53 is expressed constitutively in the postmeiotic cells of transgenic males and two lines are subfertile. Transgenic males expressing the upper level of p53 produce few spermatozoa since the majority of developing spermatids undergo apoptosis. In the subfertile males exhibiting an intermediate amount of p53, teratozoospermia is obvious suggesting an altered terminal differentiation of postmeiotic cells. In contrast lower level of p53 does not lead the third line to sterility. These results suggest that the activity of p53 is dependent in vivo on the amount of p53 present within cells, as it has been already demonstrated in vitro.

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Acknowledgements

We thank Dr Grimber for technical guidance on germ cell isolation and on TUNEL improvements and Dr Vernet for advice on spermatozoa survival, Dr Chevillard for statistical help, Drs Kahn, Lataillade and Fouquet for their essential knowledge of spermatogenesis, Drs Fouchet, Dutrillaux and Marsh for their useful critical review of this manuscript. We would also thank Dr Zelek for preliminary studies on this model. This work was supported by grants from the Association pour la Recherche sur le Cancer.

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Authors and Affiliations

  1. UMR 217 CNRS-CEA, Laboratoire de Cancérogenèse Moléculaire, DRR- DSV- CEA, BP6, 92265, Fontenay-aux-Roses, France

    Isabelle Allemand & Evelyne May

  2. Laboratoire de Cytophysiologie Analytique, Université Pierre et Marie Curie, rue Cuvier, 75006, Paris, France

    Anny Anglo & Anne-Yvonne Jeantet

  3. Institut de Recherche sur le Cancer/IFR 1221, SEAT, 7 rue Guy Moquet, BP8, 94801, Villejuif, France

    Italina Cerutti

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  1. Isabelle Allemand
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Allemand, I., Anglo, A., Jeantet, AY. et al. Testicular wild-type p53 expression in transgenic mice induces spermiogenesis alterations ranging from differentiation defects to apoptosis. Oncogene 18, 6521–6530 (1999). https://doi.org/10.1038/sj.onc.1203052

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