Male mice deficient for germ-cell cyritestin are infertile

Cyritestin is a membrane-anchored sperm protein belonging to the ADAM (a di sintegrin and a metalloprotease) family of proteins, which are proposed to be involved in cell-cell adhesion through binding to integrin receptors. Se veral lines of evidence support a role of cyritestin and other members of t his protein family in the fusion of sperm and the egg plasma membrane. In a n effort to elucidate the physiological function of cyritestin, we have dis rupted 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 th at 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 genera tion 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 .