Remodeling of the major pig xenoantigen by N-acetylglucosaminyltransferase III in transgenic pig |
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Authors: | 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 |
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Institution: | Department of Regenerative Medicine, Osaka University Graduate School of Medicine, the Genome Information Research Center, Osaka University, Suita, Osaka 565-0871, Japan. miyagawa@orgtrp.med.osaka-u.ac.jp |
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Abstract: | 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. |
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