title: α1,3-galactosyltransferase deficiency in germ-free miniature pigs increases N-glycolylneuraminic acids as the xenoantigenic determinant in pig-human xenotransplantation.
abstract: In this study, we examined whether Hanganutziu-Deicher (H-D) antigens are important as an immunogenic non-α1,3-galactose (Gal) epitope in pigs with a disrupted α1,3-galactosyltransferase gene. The targeting efficiency of the AO blood genotype was achieved (2.2%) in pig fibroblast cells. A total of 1800 somatic cell nuclear transfer (SCNT) embryos were transferred to 10 recipients. One recipient developed to term and naturally delivered two piglets. The α1,3-galactosyltransferase activity in lung, liver, spleen, and testis of heterozygote α1,3-galactosyltransferase gene knockout (GalT-KO) pigs was significantly decreased, whereas brain and heart showed very low decreasing levels of α1,3-galactosyltransferase activity when compared to those of control. Enzyme-linked lectinosorbent assay showed that the heterozygote GalT-KO pig had more sialylα2,6- and sialylα2,3-linked glycan than the control. Furthermore, the heart, liver, and kidney of the heterozygote GalT-KO pig had a higher N-glycolylneuraminic acid (Neu5Gc) content than the control, whereas the lung of the heterozygote GalT-KO pig had Neu5Gc content similar to the control. Collectively, the data strongly indicated that Neu5Gc is a more critical xenoantigen to overcoming the next acute immune rejection in pig to human xenotransplantation.
authors: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors: Jong-Yi
authors: JY
authors: Park
authors: Mi-Ryung
authors: MR
authors: Park
authors: Hong-Thuy
authors: HT
authors: Bui
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: Hosup
authors: H
authors: Shim
authors: Hye-Min
authors: HM
authors: Kim
authors: Man-Jong
authors: MJ
authors: Kang
authors: Jin-Ki
authors: JK
authors: Park
authors: Jeong-Woong
authors: JW
authors: Lee
authors: Kyung-Kwang
authors: KK
authors: Lee
authors: Jin-Hoi
authors: JH
authors: Kim
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics*; D015478:Antigens, Heterophile; D019976:Cloning, Organism; D005700:Galactosyltransferases; D055785:Gene Knockdown Techniques; D006801:Humans; D009438:Neuraminic Acids; D053652:Nuclear Transfer Techniques; D013552:Swine; D013556:Swine, Miniature; D014183:Transplantation, Heterologous
chemical_list: D015478:Antigens, Heterophile; D009438:Neuraminic Acids; C032592:N-glycolylneuraminic acid; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase