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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Remodeling of the major pig xenoantigen by N-acetylglucosaminyltransferase III in transgenic pig.

We have been successful in generating several lines of transgenic mice and pigs that contain the human beta-d-mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) gene. The overexpression of the GnT-III gene in mice and pigs reduced their antigenicity to human natural antibodies, especially the Galalpha1-3Galbeta1-4GlcNAc-R, as evidenced by immunohistochemical analysis. Endothelial cell studies from the GnT-III transgenic pigs also revealed a significant down-regulation in antigenicity, including Hanganutziu-Deicher antigen, and dramatic reductions in both the complement- and natural killer cell-mediated pig cell lyses. Changes in the enzymatic activities of other glycosyltransferases, such as alpha1,3-galactosyltransferase, GnT-IV, and GnT-V, did not support cross-talk between GnT-III and these enzymes in the transgenic animals. In addition, we demonstrated the effect of GnT-III in down-regulating the xenoantigen of pig heart grafts, using a pig to cynomolgus monkey transplantation model, suggesting that this approach may be useful in clinical xenotransplantation in the future.[1]


  1. Remodeling of the major pig xenoantigen by N-acetylglucosaminyltransferase III in transgenic pig. Miyagawa, S., Murakami, H., Takahagi, Y., Nakai, R., Yamada, M., Murase, A., Koyota, S., Koma, M., Matsunami, K., Fukuta, D., Fujimura, T., Shigehisa, T., Okabe, M., Nagashima, H., Shirakura, R., Taniguchi, N. J. Biol. Chem. (2001) [Pubmed]
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