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Anti-Xenograft Immune Responses in α1,3-Galactosyltransferase Knock-Out Mice

  • Martin J. Pearse
  • Peter J. Cowan
  • Trixie A. Shinkel
  • Choa-Guang Chen
  • Anthony J. F. d’Apice
Chapter
Part of the Subcellular Biochemistry book series (SCBI, volume 32)

Abstract

There is now an abundant of evidence (briefly reviewed below), derived from a variety of in vitro, ex vivo and in vivo studies, to demonstrate that Galactose al, 3 galactose (α-Gal) is the major xenoantigen on murine and porcine cells and tissues recognised by naturally occurring xenoantibody in human plasma (Sandrin et al., 1993; Cooper et al., 1993a; Galili et al., 1988b). The αl,3 galactosyltransferase (α1, 3GT) enzyme that forms this linkage is present in all mammals with the notable exceptions of human and Old World monkeys, in which the α1,3GT gene has been inactivated as the result of frame shift and nonsense mutations (Galili and Swanson, 1991). As a consequence of not expressing the α-Gal epitope, humans develop high titre anti-Gal antibodies (IgG, IgM and IgA) due to exposure to α-Gal on the surface ofenteric bacteria and other pathogens (Galili et al., 1988a). In order to establish a small animal model to study the role of anti-Gal antibodies in xenograft rejection we generated a line of mice lacking the α-Gal epitope by inactivating the α 1,3GT gene (Tearle et al., 1996). These mice will subsequently be referred to as GaiT KO. A similar line of mice were generated at approximately the same time by (Thall et al (1995), primarily to investigate the proposed role of the α 1,3galactosyltransferase enzyme in fertilization. The main focus of this chapter will be to review the biology ofthese mice, with particular emphasis on their application as a model to study anti-Gal antibody mediated anti-xenograft immune responses.

Keywords

Hyperacute Rejection Xenograft Rejection Cobra Venom Factor Cell Surface Glycosylation Delay Xenograft Rejection 
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Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Martin J. Pearse
    • 1
  • Peter J. Cowan
    • 1
  • Trixie A. Shinkel
    • 1
  • Choa-Guang Chen
    • 1
  • Anthony J. F. d’Apice
    • 1
  1. 1.Immunology Research CentreSt Vincent’s Hospital MelbourneFitzroyAustralia

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