Objective To explore the strategies which reduce the amount of xenoantigen Galα1

3 Gal. Methods Human α-galactosidase gene and α1

2-fucosyltransferase gene were transferred into cul-tured porcine vascular endothelial cells PEDSV.15 and human α-galactosidase transgenic mice were produced. The Galα1

3Gal on the cell surface and susceptibility of cells to human antibody-mediated lysis were analyzed. Results Human α-galactosidase gene alone reduced 78% of Galα1

3Gal on PEDSV.15 cell surface while human α-galactosidase combined with α1

2-fucosyltransferase genes removed Galα1

3Gal completely. Decrease of Galα1

3Gal could reduce susceptibility of cells to human antibody-mediated lysis

especially during co-expression of α-galactosidase gene and α1

2-fucosyltransferase gene. RT-PCR indicated positive human α-galactosidase gene expression in all organs of positive human α-galacto-sidase transgenic F1 mice including heart

liver

kidney

lung

and spleen

the amount of Galα1

3Gal antigens on which was reduced largely. 58% of spleen cells from F1 mice were destroyed by comp-lement-mediated lysis compared with 24% of those from normal mice. Conclusions Human α-galactosidase gene and α1

2-fucosyltransferase gene effectively reduce the expression of Galα1

3Gal antigens on endothelial cell surface and confers resistance to human serum-mediated cytolysis. The expression of human α-galactosidase in mice can also eliminate the Galα1

3Gal antigens in most tissues and decrease the susceptibility of spleen cells to human serum-mediated cytolysis.