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
.