Development of transgenic animals of complement regulatory molecules.

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Complement plays an essential role in the acute rejection of discordant xenotransplants. To overcome this problem, development of transgenic animals have been generated which have cDNA of the species specific membrane inhibitors of human. However, to detarmine its applicability to suppress the acute rejection of xenotransplants, experimental models of xenotransplantation between experimental animals.For this purpose, gene cloning of the species specific membrane inhibitors is an essential requirement. We have already cloned the cDNA of rat 512 antigen (512Ag) which restricts C3 convertase of rat complement. In this research project we have indentified guinea pig DAF (GP-DAF) with monoclonal antibody (mAb), and its cDNA has been successfully cloned demonstrating that GP-DAF is comprised of several isotypes due to the alternative splicing. Furthermore, we have successfully cloned cDNA of guinea pig MCP (GP-MCP), mouse DAF,mouse CD59 and rat DAF.Using these cDNA,we have prepared CHO cells transfected with cDNA of rat 512Ag, GP-DAF and GP-MCP,and these cells have been demonstrated to be registant to the serum complement homologous to the genes expressed on the transfectants.