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Delayed early embryonic lethality following disruption of the murine cyclin A2 gene

Nature Genetics volume 15, pages 8386 (1997) | Download Citation

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  • A Correction to this article was published on 01 December 1999

Abstract

In higher eukaryotes, cell cycle progression is controlled by cyclin dependent kinases (Cdks) complexed with cyclins. A-type cyclins are involved at both G1/S and G2/M transitions of the cell cycle. Cyclin A2 activates cdc2 (Cdk1) on passage into mitosis and Cdk2 at the G1/S transition1. Antisense constructs, or antibodies directed against cyclin A2 block cultured mammalian cells at both of these transitions2–4. In contrast, overexpression of cyclin A2 appears to advance S phase entry5,6 and confer anchorage-independent growth7, and can lead to apoptosis8. A second A-type cyclin, cyclin A1 has been described recently which, in the mouse, is expressed in germ cells but not somatic tissues9,10. To address the possible redundancy between different cyclins in vivo and also the control of early embryonic cell cycles, we undertook the targeted deletion of the murine cyclin A2 gene. The homozygous null mutant is embryonically lethal, demonstrating that the cyclin A2 gene is essential. Surprisingly, homozygous null mutant embryos develop normally until post-implantation, around day 5.5 p.c. This observation may be explained by the persistence of a maternal pool of cyclin A2 protein until at least the blastocyst stage, or an unexpected role for cyclin A1 during early embryo development.

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Author information

Affiliations

  1. Institut National de la Santé et de la Recherche Médicale, Unité 370, Faculté Necker, 156 rue de Vaugirard, 75015 Paris, France.

    • Martin Murphy
    • , Catherine Senamaud-Beaufort
    • , Nicola J. Winston
    • , Christian Bréchot
    •  & Joëlle Sobczak-Thépot
  2. Institut National de la Recherche Agronomique, Laboratoire de Génétique Biochimique, Jouy-en-Josas, France.

    • Marie-Georges Stinnakre
  3. University of Cambridge, Department of Biochemistry, Cambridge, CB21QW, England, UK.

    • Claire Sweeney
    •  & Mark Carrington
  4. The Babraham Institute, Cambridge, CB2 4AT, England, UK.

    • Michal Kubelka
  5. Permanent address: Institute of Animal Physiology and Genetics, Dept of Genetics, Academy of Sciences of the Czech Republic, 27721 Libechov, Czech Republic.

    • Michal Kubelka
  6. at lNSERM U370, Faculté Necker, 156 rue de Vaugirard, 75730 Paris cedex 15, France.

    • Joëlle Sobczak-Thépot

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DOI

https://doi.org/10.1038/ng0197-83

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