Male Mice Deficient for Germ-Cell Cyritestin Are Infertile1

  1. Rahman Shamsadin3,
  2. Ibrahim M. Adham3,
  3. Karim Nayernia3,
  4. Uwe A.O. Heinlein4,
  5. Heike Oberwinkler3 and
  6. Wolfgang Engel2,,3
  1. Institute of Human Genetics,3 University of Göttingen, D-37073 Göttingen, Germany
  2. Institute of Genetics,4 University of Düsseldorf, D-40225 Düsseldorf, Germany

    Abstract

    Cyritestin is a membrane-anchored sperm protein belonging to the ADAM (Formula Formulaisintegrin and Formula Formulaetalloprotease) family of proteins, which are proposed to be involved in cell-cell adhesion through binding to integrin receptors. Several lines of evidence support a role of cyritestin and other members of this protein family in the fusion of sperm and the egg plasma membrane. In an effort to elucidate the physiological function of cyritestin, we have disrupted its locus by homologous recombination. Male homozygous null mutants are infertile, even though spermatogenesis, mating, and migration of sperm from the uterus into the oviduct are normal. In vitro experiments showed that infertility is due to the inability of the cyritestin-deficient sperm to bind to the zona pellucida. However, after removal of the zona pellucida, sperm-egg membrane fusion monitored by the presence of pronuclei and generation of 2- and 4-cell embryos did not reveal any differences from the wild-type situation. These results demonstrate that cyritestin is crucial in the fertilization process at the level of the sperm-zona pellucida interaction.

    Footnotes

    • 1 This work was supported by the Deutsche Forschungsgemeinschaft to I.M.A. and W.E. (SFB 271) and to U.A.O.H. (He 1581/4-2).

    • 2 Correspondence: Wolfgang Engel, Institute of Human Genetics Gosslerstrasse 12d, D-37073 Göttingen, Germany. FAX: 49 551 399303; wengel{at}gwdg.de

      • Accepted July 20, 1999.
      • Received April 22, 1999.
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