The zona pellucida: using molecular genetics to study the mammalian egg coat

An extracellular matrix that mediates critical steps in fertilization and early development surrounds all vertebrate eggs. In mice and humans, this matrix is known as the zona pellucida and comprises three glycoproteins: ZP1, ZP2 and ZP3. Homologues of these proteins isolated from other vertebrates have conserved protein motifs that may be important for establishing a common fibrillar structure. However, specific but contradictory biological roles have been assigned to individual egg coat proteins based on assays in vitro in a wide range of species. Mouse lines lacking either ZP1 or ZP3 have been established with abnormal or absent zona matrices and varying degrees of infertility to examine zona structure and function in vivo. By crossing mouse lines lacking individual zona proteins with those expressing human homologues, the structural integrity of the zona matrix can be restored. Because mouse and human spermatozoa exhibit order-specific binding to the zona pellucida, mice with 'humanized' chimaeric zonae may provide an experimental system to elucidate the molecular basis of sperm-zona interaction.