DOWN-REGULATION OF Gal??(1,3)Gal EXPRESSION BY ??1,2-FUCOSYLTRANSFERASE

Abstract

Background. In pig-to-primate transplantation, antibody-mediated hyperacute rejection is the consequence of binding of natural antibodies to Galα(1,3)Gal on pig endothelium. The elimination of the Galα(1,3)Gal antigen from pig cells should prevent hyperacute rejection. Using in vitro techniques, we have previously reported that using the α1,2-fucosyltransferase gene induces the preferential expression of H substance with a concomitant reduction in the expression of Galα(1,3)Gal. The aim of the present study was to examine the effect of expressing the α1,2-fucosyltransferase gene in vivo on Galα(1,3)Gal. Methods. Three α1,2-fucosyltransferase transgenic lines of mice were produced and characterized serologically and histologically. Results. Immunohistological studies showed heavy staining for H substance in liver, spleen, kidney, and heart, with a reduction in staining for Galα(1,3)Gal. In addition, there was a reduction in the binding of human anti-Galα(1,3)Gal antibody to lymphocytes from α1,2-fucosyltransferase transgenic mice and a substantial decrease in complement-mediated cytolysis of α1,2-fucosyltransferase transgenic lymphocytes when compared with that obtained with normal mice. Conclusions. The findings have important implications, in that α1,2-fucosyltransferase transgenic pigs could be produced as a source for humans. Such pigs should have a reduced expression of Galα(1,3)Gal.