Introduction of α(1,2)‐fucosyltransferase and its effect on a‐Gal epitopes in transgenic pig

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Abstract
Hyperacute rejection (from pig to human) is thought to result from activation of complement initiated by the binding of host natural antibodies to α‐galactosyl (α‐Gal) epitopes of donor endothelial cells. However, α‐Gal epitope shares a common precursor with H antigen in humans. This means that H antigens as well as α‐Gal epitopes are synthesized in a competitive manner by different enzymes. We thought that it would be possible to convert α‐Gal epitopes into H antigens by introducing cDNA of α(1,2)‐fucosyltransferase (α1–2FT) into porcine cells, and so, pig embryos were microinjected with αl‐2FT cDNA. Transgenic pigs that carried α1–2FT were thus established. Cytotoxicity of fibrocytes derived from skin of transgenic pig was measured by 51Cr release assay, which showed that H antigen‐expressing cells were significantly resistant to a challenge with human sera. These experiments indicate that our method provides a new strategy which contributes to a successful discordant xenotransplantation.