Development of model animal to reveal the antibody production for ABO blood group antigens.

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Histo-blood group ABH antigens are important not only for blood transfusion but also for organ transplantation. To improve the clinical management of transplantation, we have established transgenic rats expressing human A-transferase and B-transferase gene. Wild Wistar rats expressed A-antigen in salivary gland, intestine, and urinary bladder tissue, but B-antigen was not stained in any organs studied. A-transgenic rats expressed A-antigen in ectopic tissue of the brain plexus, type II lung epithelium, pancreas, and epidermis. B-antigen in the B-transgenic rat was expressed in the same organs as A-transgenic rats. When small intestines of wild Wistar were transplanted into A- or B-trangenic rats, the grafts were rapidly rejected compared to the grafts from A- or B-transgenic rats into wild. The systemic expression of A- or B-antigens may have modified the terminal organization of sugar chain antenna and have stimulated the innate-immune system. We have cloned authologous genes of ABO transferase from Wistar rat, which consisted of three A-transferase and one B-transferase genes. These cDNAs were mapped on rats genome draft sequence. Rat chromosome 1 accommodates B-transferase gene and chromosome 3 encodes tandem arrayed three A-transferase copies. These facts indicated that the A- and B-transferase genes were established as paralogous genes in some mammals. Primates encode single ABO gene. If the ABO ancestral genes consisted of multicopy genes with A and B transferase activity like rats, they must donate or accept gene fragments from each other and may produce a locus composed of A-alleles and B-alleles. The multicopy genes may possibly gather and bundle into a single gene through unequal cross over. This estimation must be resolved by further genome projects in other mammals.