alpha 1,3-Galactosyltransferase Deficiency in Germ-Free Miniature Pigs Increases N-Glycolylneuraminic Acids As the Xenoantigenic Determinant in Pig-Human Xenotransplantation

作者：Park Jong Yi; Park Mi Ryung; Bui Hong Thuy; Kwon Deug Nam; Kang Min Hui; Oh Mihye; Han Jae Woong; Cho Ssang Goo; Park Chankyu; Shim Hosup; Kim Hye Min; Kang Man Jong; Park Jin Ki; Lee Jeong Woong; Lee Kyung Kwang; Kim Jin Hoi^*

来源：Cellular Reprogramming, 2012, 14(4): 353-363.

DOI：10.1089/cell.2011.0083

In this study, we examined whether Hanganutziu-Deicher (H-D) antigens are important as an immunogenic non-alpha 1,3-galactose (Gal) epitope in pigs with a disrupted alpha 1,3-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 alpha 1,3-galactosyltransferase activity in lung, liver, spleen, and testis of heterozygote alpha 1,3-galactosyltransferase gene knockout (GalT-KO) pigs was significantly decreased, whereas brain and heart showed very low decreasing levels of alpha 1,3-galactosyltransferase activity when compared to those of control. Enzyme-linked lectinosorbent assay showed that the heterozygote GalT-KO pig had more sialyl alpha 2,6- and sialyl alpha 2,3-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.

• 出版日期2012-8