Transgenic expression of human alpha1,2-fucosyltransferase (H-transferase) prolongs mouse heart survival in an ex vivo model of xenograft rejection

Transplantation
C G ChenM J Pearse

Abstract

The expression of human alpha1,2-fucosyltransferase (H-transferase, HT) has been proposed as an alternative strategy to alpha1,3-galactosyltransferase (GT) gene knockout, which is not currently feasible in pigs, to reduce the galactose-alpha1,3-galactose (Gal) epitope expression. HT expression has recently been shown in transgenic mice and pigs to significantly reduce Gal expression on a variety of cells; however, its ability to do so on endothelial cells and its effectiveness at prolonging xenograft survival are yet to be determined. HT-transgenic, Gal knockout (Gal KO) mice, and mice containing both genetic modifications (HT-transgenic/Gal KO) were tested for H-substance and Gal expression on splenocytes and endothelial cells by flow cytometric analysis. In addition, the hearts of these mice were perfused ex vivo with 6% human plasma, and the effect on cardiac function was determined. H-substance expression was detected on both splenocytes and endothelial cells of HT-transgenic mice. The level of H-substance expression was not affected by the presence or absence of GT in the cells, consistent with HT being dominant over GT. The ability of HT expression to reduce Gal expression was highly variable depending on the cell type. G...Continue Reading

References

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Citations

Dec 21, 2000·Journal of Immunological Methods·S D LoveW Parker
Mar 20, 1999·Transplantation Proceedings·J M GrinyoJ Torras
Dec 2, 1999·Biochimica Et Biophysica Acta·T Hennet, L G Ellies
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Nov 4, 2000·Transplantation·I F McKenzieM S Sandrin
Oct 4, 2008·Current Opinion in Hematology·Eldad A HodSteven L Spitalnik
Dec 16, 1998·Xenotransplantation·M Koulmanda, H Auchincloss
May 26, 2004·Transplant Immunology·Mark SaylesRoger A Barker
Dec 4, 2010·Transplantation Reviews·Hilton GockPeter Cowan
Jun 2, 2010·Clinics in Laboratory Medicine·David K C CooperMark Yazer
Sep 4, 2008·Transplant International : Official Journal of the European Society for Organ Transplantation·Hidetaka HaraDavid K C Cooper
Mar 13, 2008·Xenotransplantation·Lisa Murray-SegalAnthony J F d'Apice
Dec 12, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Cristina CostaWilliam L Fodor
Oct 3, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C CostaW L Fodor

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