The gamete fusion process is defective in eggs of Cd9-deficient mice

The cell-surface molecule Cd9, a member of the transmembrane-4 superfamily( 1), interacts with the integrin family(2) and other membrane proteins(3-5), and is postulated to participate in cell migration and adhesion(6-8). Expr ession of Cd9 enhances membrane fusion between muscle cells(9) and promotes viral infection in some cells(10,11). 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 equatori al region of the sperm head(12). The fused membrane is then disrupted, and the sperm nucleus as well as the cytoplasm is incorporated into the egg. Cd 9 is expressed on the plasma membrane of the mouse egg, and an anti-Cd9 mon oclonal antibody inhibits sperm-egg surface interactions(13). We generated Cd9(-/-) mice and found that homozygous mutant females were infertile. Sper m-egg binding was normal, but sperm-egg fusion was almost entirely inhibite d in eggs from Cd9(-/-) females. Intracellular Ca2+ oscillations, which sig nal fertilization, were absent in almost all mutant eggs; in rare cases, a response occurred after a long time period. In normal animals, Cd9 molecule s were expressed on the egg microvilli and became densely concentrated at t he sperm attachment site. Thus, our results show that Cd9 is important in t he gamete fusion process at fertilization.