title: Alpha 1,3-galactosyltransferase deficiency in pigs increases sialyltransferase activities that potentially raise non-gal xenoantigenicity.
abstract: 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 [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. 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 α-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 α2,6-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.
authors: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Jong-Yi
authors: JY
authors: Park
authors: Mi-Ryung
authors: MR
authors: Park
authors: Deug-Nam
authors: DN
authors: Kwon
authors: Min-Hui
authors: MH
authors: Kang
authors: Mihye
authors: M
authors: Oh
authors: Jae-Woong
authors: JW
authors: Han
authors: Ssang-Goo
authors: SG
authors: Cho
authors: Chankyu
authors: C
authors: Park
authors: Dong-Ku
authors: DK
authors: Kim
authors: Hyuk
authors: H
authors: Song
authors: Jae-Wook
authors: JW
authors: Oh
authors: Jin-Hoi
authors: JH
authors: Kim
mesh_terms: D000818:Animals; D015478:Antigens, Heterophile / Q000378:metabolism*; D000939:Epitopes / Q000378:metabolism; D005700:Galactosyltransferases / Q000172:deficiency* / Q000235:genetics; D017353:Gene Deletion; D006001:Glycoconjugates / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D009438:Neuraminic Acids / Q000378:metabolism; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism*; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D013552:Swine / Q000235:genetics / Q000378:metabolism*; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D015478:Antigens, Heterophile; D000939:Epitopes; D006001:Glycoconjugates; D006023:Glycoproteins; D009438:Neuraminic Acids; C032592:N-glycolylneuraminic acid; D006899:Mixed Function Oxygenases; D007521:Isocitrate Dehydrogenase; C074383:CMPacetylneuraminate monooxygenase; D005700:Galactosyltransferases; C530267:alpha-1,3-galactosyltransferase 1, porcine; D012799:Sialyltransferases; C069715:trans-sialidase; D009439:Neuraminidase; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase