The present invention relates to a transgenic swine with an inhibited immune rejection response during a xeno- transplantation which simultaneously expresses a Heme oxygenase (HO-1) gene and a tumor necrosis factor receptor 1-Fc (TNFR1-Fc) gene and in which an α-1,3-galactosyltransferase (GGTA1) gene and a cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene are knocked out, and to a method for manufacturing the same. The transgenic swine which simultaneously expresses human HO-1 and TNFR1-Fc fusion genes and in which a GGTA1 gene and a CMAH gene are knocked out of the present invention can reduce oxidative stress during long-term separation and in vitro culturing by anti-oxidation actions and cell protection functions of the HO-1 gene, can reduce TNF-α-mediated inflammatory responses occurring at the beginning of transplantation by TNFR1-Fc expression, and can reduce acute vascular rejection responses by inhibiting maturation of dendritic cells and regulating proliferation and activation of T cells, thereby promoting initial engraftment of transplanted organs. Furthermore, it is possible to improve the survival rate of transplanted organs by inhibiting hyperacute immune rejection responses by GGTA1 and acute immune responses by CMAH. Therefore, it is possible to produce an organ in which an immune rejection response is inhibited when heterotransplantation is performed by using the transgenic swine.본 발명은 HO-1 (Heme oxygenase-1) 유전자 및 TNFR1-Fc (Tumor necrosis factor receptor 1-Fc) 유전자를 동시에 발현하며 GGTA1 (α-1,3-galactosyltransferase) 유전자 및 CMAH (cytidine monophosphate-N-acetylneuraminic acid hydroxylase) 유전자가 넉아웃 (knock-out)된, 이종 장기 이식 시 면역 거부 반응이 억제된 형질전환 돼지, 및 이의 제조방법에 관한 것이다.본 발명의 인간 HO-1과 TNFR1-Fc 융합 유전자를 동시 발현하며 GGTA1 유전자 및 CMAH 유전자가 넉아웃된 형질전환 돼지는 HO-1 유전자의 항산화 작용 및 세포 보호 기능 등에 의해 장기 분리 및 체외 배양 시에 산화적 스트레스를 감소시킬 수 있고, TNFR1-Fc 발현에 의해 이식 초기에 일어나는 TNF-α 매개의 염증 반응도 감소시킬 수 있으며, 또한 수지상 세포의 성숙을 억제하고 T 세포의 증식과 활성화를 조절하여 급성 혈관계 거부 반응을 감소시켜 이식된 장기의 초기 생착을 촉
