Transgenic pig which simultaneously expresses HO-1 gene and TNFR1-Fc gene, and comprises knocked-out GGTA1 gene, and use thereof

A transgenic pig comprising in its genome (i) an exogenous nucleic acid encoding a human heme oxygenase-1 (HO-1) gene;

• (ii) an exogenous nucleic acid encoding a human tumor necrosis factor receptor 1 fusion protein (TNFR1-Fc);
• and (iii) a homozygous disruption of the endogenous gene encoding alpha-1,3, galactosyltransferase (GGTA1), wherein the transgenic pig simultaneously expresses the HO-1 and TNFR1-Fc and lacks expression of the GGTA1, and wherein (i) cells of the transgenic pig have greater resistance to apoptotic and oxidative stress stimulation compared to wild type cells;
• (ii) cells are more resistant to the human serum and complement compared to those derived from a transgenic pigs comprising in its genome exogenous nucleic acids encoding HO-1 and TNFR1-Fc but the endogenous GGTA1 is intact;
• and (iii) the antibody/complement-mediated lytic reaction is significantly reduced compared to the transgenic pigs comprising in its genome exogenous nucleic acids encoding HO-1 and TNFR1-Fc but the endogenous GGTA1 is intact.