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 gl ycoprotein ZP3 on murine oocytes, This trisaccharide has been implicat ed 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 synthe sis and expression, These mice develop normally and exhibit no gross p henotypic abnormalities. The Gal alpha 1-3Gal epitope is absent from t he vascular endothelium and other tissues in alpha 1,3GT (-/-) adult m ice. By contrast, alpha 1,3GT (-/-) mice, like humans, develop natural ly occurring anti-alpha-galactoside antibodies normally absent in wild type mice, Female alpha 1,3GT (-/-) mice yield oocytes that are devoi d of the Ga alpha 1-->3Gal epitope; however, these mice are fully fert ile, These observations indicate that the Gal alpha 1-->3Gal moiety is not essential to sperm-oocyte interactions leading to fertilization o r 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 m ajor barrier to the use of porcine and other non-primate organs for xe notransplantation in humans.