Nature Genetics
24, 279 - 282 (2000)
doi:10.1038/73502
The gamete fusion process is defective in eggs of Cd9-deficient miceKeisuke Kaji1, Shoji Oda2, Tomohide Shikano2, Tatsuya Ohnuki3, Yoshikatsu Uematsu3, Junko Sakagami3, Norihiro Tada3, Shunichi Miyazaki2, 4
& Akira Kudo11
Department of Life Science, Tokyo Institute of Technology, Yokohama, Japan
2
Department of Physiology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
3
Medicinal Research Laboratories, Taisho Pharmaceutical Co., Omiya, Japan
4
Laboratory of Intracellular Metabolism, Department of Molecular Physiology, National Institute for Physiological Sciences, Okazaki, Japan
Correspondence should be addressed to Akira Kudo akudo@bio.titech.ac.jpThe cell-surface molecule Cd9, a member of the transmembrane-4 superfamily1, interacts with the integrin family2 and other membrane proteins3,
4,
5, and is postulated to participate in cell migration and adhesion6,
7,
8. Expression of Cd9 enhances membrane fusion between muscle cells9 and promotes viral infection in some cells10,
11. Fertilization also involves membrane fusion, between gametes. In mammals, the sperm binds to microvilli on the egg surface, and sperm-egg membrane fusion first occurs around the equatorial region of the sperm head12. The fused membrane is then disrupted, and the sperm nucleus as well as the cytoplasm is incorporated into the egg. Cd9 is expressed on the plasma membrane of the mouse egg, and an anti-Cd9 monoclonal antibody inhibits sperm-egg surface interactions13. We generated Cd9
-/- mice and found that homozygous mutant females were infertile. Sperm-egg binding was normal, but sperm-egg fusion was almost entirely inhibited in eggs from Cd9
-/- females. Intracellular Ca2+ oscillations, which signal fertilization, were absent in almost all mutant eggs; in rare cases, a response occurred after a long time period. In normal animals, Cd9 molecules were expressed on the egg microvilli and became densely concentrated at the sperm attachment site. Thus, our results show that Cd9 is important in the gamete fusion process at fertilization.
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