The present invention provides porcine isogloboside 3 (iGb3) synthase protein, cDNA, and genomic DNA regulatory sequence. The present also invention includes porcine animals, tissue and organs as well as cells and cell lines derived from such animals, tissue and organs, which lack expression of functional iGb3 synthase. Such animals, tissues, organs and cells can be used in research and in medical therapy, including xenotransplantation. In addition, methods are provided to prepare organs, tissues, and cells lacking the porcine iGb.sub.3 synthase gene for use in xenotransplantation.