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KMID : 1023620110350040511
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Reproductive and Developmental Biology
2011 Volume.35 No. 4 p.511 ~ p.518
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Alpha 1,3-Galactosyltransferase Deficiency in Miniature Pigs Increases Non-Gal Xenoantigens
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Min Gye-Sik
Park Jong-Yi
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Abstract
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To avoid hyperacute rejection of xenografts, α1,3-galactosyltransferase knock-out (GalT KO) pigs have been produced.
In this study, we examined whether Sia-containing glycoconjugates are important as an immunogenic non-Gal
epitope in the pig liver with disruption of α1,3-galactosyltransferase gene. The target cells were then used as donor
cells for somatic cell nuclear transfer (scNT). A total of 1,800 scNT embryos were transferred to 10 recipients. One
recipient developed to term and naturally delivered two piglets. Real-time RT-PCR and glycosyltransferase activity
showed that α2,3-sialyltransferase (α2,3ST) and α2,6-sialyltransferase (α2,6ST) in the heterozygote GalT KO liver
have higher expression levels and activities compared to controls, respectively. According to lectin blotting, sialic acidcontaining glycoconjugate epitopes were also increased due to the decreasing of α-Gal in heterozygote GalT KO liver,
whereas GalNAc-containing glycoconjugate epitopes were decreased in heterozygote GalT KO liver compare to the
control. Furthermore, the heterozygote GalT KO liver showed a higher Neu5Gc content than control. Taken together,
these finding suggested that the deficiency of GalT gene in pigs resulted in increased production of Neu5Gc-bounded
epitopes (H-D antigen) due to increase of α2,6-sialyltransferase. Thus, this finding suggested that the deletion of
CMAH gene to the GalT KO background is expected to further prolong xenograft survival.
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KEYWORD
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α-Gal, H-D antigens, Tn-antigen, Xenotransplantation, Pig, GalT KO, Somatic cell nuclear transfer
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