Alpha 1,3-Galactosyltransferase Deficiency in Pigs Increases Sialyltransferase Activities That Potentially Raise Non-Gal Xenoantigenicity

作者:Park Jong Yi; Park Mi Ryung; Deug Nam Kwon; Kang Min Hui; Oh Mihye; Han Jae Woong; Cho Ssang Goo; Park Chankyu; Kim Dong Ku; Song Hyuk; Oh Jae Wook; Kim Jin Hoi*
来源:Journal of Biomedicine and Biotechnology, 2011, 560850.
DOI:10.1155/2011/560850

摘要

We examined whether deficiency of the GGTA1 gene in pigs altered the expression of several glycosyltransferase genes. Real-time RT-PCR and glycosyltransferase activity showed that 2 sialyltransferases [alpha 2,3-sialyltransferase (alpha 2,3ST) and alpha 2,6-sialyltransferase (alpha 2,6ST)] in the heterozygote GalT KO liver have higher expression levels and activities compared to controls. Enzyme-linked lectin assays indicated that there were also more sialic acid-containing glycoconjugate epitopes in GalT KO livers than in controls. The elevated level of sialic-acid-containing glycoconjugate epitopes was due to the low level of alpha-Gal in heterozygote GalT KO livers. Furthermore, proteomics analysis showed that heterozygote GalT KO pigs had a higher expression of NAD(+)-isocitrate dehydrogenase (IDH), which is related to the CMP-N-acetylneuraminic acid hydroxylase (CMAH) enzyme reaction. These findings suggest the deficiency of GGTA1 gene in pigs results in increased production of N-glycolylneuraminic acid (Neu5Gc) due to an increase of alpha 2,6-sialyltransferase and a CMAH cofactor, NAD(+)-IDH. This indicates that Neu5Gc may be a critical xenoantigen. The deletion of the CMAH gene in the GalT KO background is expected to further prolong xenograft survival.

  • 出版日期2011

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