Ggta1, encoding α1,3-galactosyltransferase, is crucial for the biosynthesis of galactosyl-alpha 1,3-galactose, the major xenoantigen causing hyperacute rejection in xenotransplantation [3]. It regulates the expression of the carbohydrate epitope Galα1-3Galβ1-4GlcNAc-R, known as the α-Gal antigen, which is a primary xenoantigen recognized by the human immune system [1].

In gene-editing studies, GGTA1-KO pigs and rabbits have been developed. In rabbits, the mutation efficiency of GGTA1 gene-editing using the CRISPR/Cas9 system was as high as 92.3% in F0 pups, and α-Gal antigen expression in major organs decreased by over 99.96% compared to wild-type rabbits [1]. In pigs, genetic knockout of GGTA1 removes the immunogenic α-Gal epitope, but may lead to the emergence of neo-glycans, changing the distribution and levels of other porcine glycans [2]. Also, in GGTA1-KO pigs, N-glycans capped with Neu5Gc were increased compared to wild-type pigs [2].

In conclusion, GGTA1 plays a central role in the immunogenicity of xenografts due to its role in synthesizing the α-Gal antigen. The generation of GGTA1-KO animal models, especially pigs and rabbits, has significantly contributed to understanding the immunological mechanisms in xenotransplantation, aiming to overcome the immunological rejection hurdles in pig-to-human organ transplantation [1,2,3].