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

Reduction of the Gal-alpha1,3-Gal epitope of mouse endothelial cells by transfection with the N-acetylglucosaminyltransferase III gene.

In order to prevent hyperacute rejection in pig-to-human xenotransplantation, it would be very useful to be able to down-regulate the Gal alpha1-3 Galbeta 1-4 GlcNAc-R (alpha-Gal epitope) in mouse and swine tissues. When the beta-D-mannoside beta-1,4-N-acetylglucosaminyl-transferase III (GnT-III) gene was introduced into mouse aorta endothelial cells (MEC) their susceptibility to complement-mediated cell lysis by normal human serum (NHS) was reduced. Expression of GnT-III also suppressed the antigenicity of MEC to human natural antibodies as shown by binding of Griffonia simplicifolia 1 isolectin (GS1B4 lectin) to the alpha-Gal epitope. Western blot analysis indicated that the reactivity of the glycoproteins of the transfectants to NHS and GSIB4 lectin was reduced to approximately the same extent. Thus GnT-III, a key enzyme involved in the formation of branched N-linked sugars, reduces the expression of xenoantigens, suggesting that this approach may be of value in clinical xenotransplantation.[1]


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