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Publication : The alpha-1,3-galactosyltransferase knockout mouse. Implications for xenotransplantation.

First Author  Tearle RG Year  1996
Journal  Transplantation Volume  61
Issue  1 Pages  13-9
PubMed ID  8560551 Mgi Jnum  J:288220
Mgi Id  MGI:6430913 Doi  10.1097/00007890-199601150-00004
Citation  Tearle RG, et al. (1996) The alpha-1,3-galactosyltransferase knockout mouse. Implications for xenotransplantation. Transplantation 61(1):13-9
abstractText  Organ xenografts in discordant combinations such as pig-to-man undergo hyperacute rejection due to the presence of naturally occurring human anti-pig xenoantibodies. The galactose alpha(1,3)-galactose epitope on glycolipids and glycoproteins is the major porcine xenoantigen recognized by these xenoantibodies. This epitope is formed by alpha(1,3)-galactosyltransferase, which is present in all mammals except man, apes, and Old World monkeys. We have generated mice lacking this major xenoantigen by inactivating the alpha(1,3)-galactosyltransferase gene. These mice are viable and have normal organs but develop cataracts. Substantially less xenoantibody from human serum binds to cells and tissues of these mice compared with normal mice. Similarly, there is less activation of human complement on cells from mice lacking the galactose alpha(1,3)-galactose epitope. These mice confirm the importance of the galactose alpha(1,3)-galactose epitope in human xenoreactivity and the logic of continuing efforts to generate pigs that lack this epitope as a source of donor organs.
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