1. α1,3-Galactosyltransferase Deficiency in Germ-Free Miniature Pigs IncreasesN-Glycolylneuraminic Acids As the Xenoantigenic Determinant in Pig–Human Xenotransplantation
- Author
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Chankyu Park, Jeong-Woong Lee, Hye-Min Kim, Jin-Hoi Kim, Jae-Woong Han, Mihye Oh, Jong-Yi Park, Hosup Shim, Hong-Thuy Bui, Ssang-Goo Cho, M J Kang, Kyung-Kwang Lee, Mi-Ryung Park, Man-Jong Kang, Jin-Ki Park, and Deug-Nam Kwon
- Subjects
Nuclear Transfer Techniques ,Swine ,Cloning, Organism ,Xenotransplantation ,medicine.medical_treatment ,Transplantation, Heterologous ,Spleen ,Biology ,Epitope ,Animals, Genetically Modified ,Andrology ,Antigens, Heterophile ,medicine ,Animals ,Humans ,Gene knockout ,Kidney ,Heterozygote advantage ,Cell Biology ,Galactosyltransferases ,Transplantation ,medicine.anatomical_structure ,Gene Knockdown Techniques ,Immunology ,Swine, Miniature ,Somatic cell nuclear transfer ,Neuraminic Acids ,Developmental Biology ,Biotechnology - 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.
- Published
- 2012
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