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Journal of Animal and Veterinary Advances
Year: 2014  |  Volume: 13  |  Issue: 10  |  Page No.: 616 - 622

Production of Wuzhishan Miniature Pigs Expressing High-Level Human CD46

Shen He, Chong Feng, Chuan Long, Hongmei Pan, Ning Wang, Ningning Shi, Fei Wang, Yanrong Zhou, Hongxing Chen, Mingxing Chu, Dengke Pan and Xuewei Li    

Abstract: The development of α-1,3-galactosyltransferase gene knockout pigs along with overexpression of human Complement Regulatory Proteins (hCRPs) has been an important step in overcoming hyperacute rejection when pig organs are transplanted into nonhuman primates. Most previous studies have used commercial pigs as organ donors. However, little has been reported about the use of inbred miniature pigs as genetic donors expressing hCRPs. As expression of hCRP on the surface of pig cells, especially human membrane cofactor protein (hCD46) could effectively protect them against human complement-mediated rejection, researchers constructed an engineered hCD46 minigene expression vector and generated transgenic Wuzhishan miniature Pigs (WZSP) expressing hCD46. Expression of hCD46 with a distinct tissue-specific pattern similar to the human one was observed using immunohistochemistry. Various tissues revealed strong immunostaining in most epithelial tissues and vascular endothelium. Flow cytometry analysis of hCD46 porcine AECs showed expression levels similar to human AECs. Complement-mediated cytolysis of transgenic porcine Aortic Endothelial Cells (AECs) with human serum showed significant protection. Distinct differences between ABO blood groups were also observed with much less cytolysis of porcine AECs treated with B blood group serum than with other serum types. In conclusion, transgenic WZSPs with sufficient expression of hCD46 have been established successfully and will facilitate further xenotransplantation research.

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