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    The molecular basis for Gal alpha(1,3)Gal expression in animals with a deletion of the alpha 1,3galactosyltransferase gene

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    Author
    Milland, J; Christiansen, D; Lazarus, BD; Taylor, SG; Xing, PX; Sandrin, MS
    Date
    2006-02-15
    Source Title
    JOURNAL OF IMMUNOLOGY
    Publisher
    AMER ASSOC IMMUNOLOGISTS
    University of Melbourne Author/s
    Christiansen, Dale; Sandrin, Mauro; MILLAND, JULIE; TAYLOR, SIMON GRANT
    Affiliation
    Surgery - Austin Health And Northern Health
    Metadata
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    Document Type
    Journal Article
    Citations
    Milland, J., Christiansen, D., Lazarus, B. D., Taylor, S. G., Xing, P. X. & Sandrin, M. S. (2006). The molecular basis for Gal alpha(1,3)Gal expression in animals with a deletion of the alpha 1,3galactosyltransferase gene. JOURNAL OF IMMUNOLOGY, 176 (4), pp.2448-2454. https://doi.org/10.4049/jimmunol.176.4.2448.
    Access Status
    This item is currently not available from this repository
    URI
    http://hdl.handle.net/11343/26266
    DOI
    10.4049/jimmunol.176.4.2448
    Description

    C1 - Journal Articles Refereed

    Abstract
    The production of homozygous pigs with a disruption in the GGTA1 gene, which encodes alpha1,3galactosyltransferase (alpha1,3GT), represented a critical step toward the clinical reality of xenotransplantation. Unexpectedly, the predicted complete elimination of the immunogenic Galalpha(1,3)Gal carbohydrate epitope was not observed as Galalpha(1,3)Gal staining was still present in tissues from GGTA1(-/-) animals. This shows that, contrary to previous dogma, alpha1,3GT is not the only enzyme able to synthesize Galalpha(1,3)Gal. As iGb3 synthase (iGb3S) is a candidate glycosyltransferase, we cloned iGb3S cDNA from GGTA1(-/-) mouse thymus and confirmed mRNA expression in both mouse and pig tissues. The mouse iGb3S gene exhibits alternative splicing of exons that results in a markedly different cytoplasmic tail compared with the rat gene. Transfection of iGb3S cDNA resulted in high levels of cell surface Galalpha(1,3)Gal synthesized via the isoglobo series pathway, thus demonstrating that mouse iGb3S is an additional enzyme capable of synthesizing the xenoreactive Galalpha(1,3)Gal epitope. Galalpha(1,3)Gal synthesized by iGb3S, in contrast to alpha1,3GT, was resistant to down-regulation by competition with alpha1,2fucosyltransferase. Moreover, Galalpha(1,3)Gal synthesized by iGb3S was immunogenic and elicited Abs in GGTA1 (-/-) mice. Galalpha(1,3)Gal synthesized by iGb3S may affect survival of pig transplants in humans, and deletion of this gene, or modification of its product, warrants consideration.
    Keywords
    Transplantation Immunology ; Immune System and Allergy

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