OOCYTE GAL-ALPHA-1,3GAL EPITOPES IMPLICATED IN SPERM ADHESION TO THE ZONA-PELLUCIDA GLYCOPROTEIN ZP3 ARE NOT REQUIRED FOR FERTILIZATION IN THE MOUSE

The Gal alpha 1-->3Gal structure is displayed on the zona pellucida glycoprotein ZP3 on murine oocytes, This trisaccharide has been implicated in sperm-zona pellucida adhesive events thought to be essential to fertilization in the mouse. To determine directly if this molecule is required for fertilization, we have generated mice that are deficient in a gene (alpha 1,3GT) encoding the UDP-Gal:beta-D-Gal-alpha 1-->3Ga-galactosyltransferase enzyme responsible for Gal alpha 1-->3Gal synthesis and expression, These mice develop normally and exhibit no gross phenotypic abnormalities. The Gal alpha 1-3Gal epitope is absent from the vascular endothelium and other tissues in alpha 1,3GT (-/-) adult mice. By contrast, alpha 1,3GT (-/-) mice, like humans, develop naturally occurring anti-alpha-galactoside antibodies normally absent in wild type mice, Female alpha 1,3GT (-/-) mice yield oocytes that are devoid of the Ga alpha 1-->3Gal epitope; however, these mice are fully fertile, These observations indicate that the Gal alpha 1-->3Gal moiety is not essential to sperm-oocyte interactions leading to fertilization or to essentially normal development, They further suggest that alpha 1,3GT (-/-) mice will find utility for exploring approaches to diminish anti-Gal-dependent hyperacute xenograft rejection, which presents a major barrier to the use of porcine and other non-primate organs for xenotransplantation in humans.