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Research Project: Validate Causative Mutations in Agriculturally-Important Vertebrates

Location: Plant Genetics Research

Title: Impact of gene duplication of B4GALNT2 in pigs for xenotransplantation- technical & practical

Author
item LUCAS, CAROL - University Of Missouri
item WHITWORTH, KRISTIN - University Of Missouri
item SAMUEL, MELISSA - University Of Missouri
item Redel, Bethany
item PRATHER, RANDALL - University Of Missouri
item WELLS, KEVIN - University Of Missouri

Submitted to: Xenotransplantation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/6/2026
Publication Date: 3/18/2026
Citation: Lucas, C.G., Whitworth, K.M., Samuel, M.S., Redel, B.K., Prather, R.S., Wells, K.D. 2026. Impact of gene duplication of B4GALNT2 in pigs for xenotransplantation- technical & practical. Xenotransplantation. 33(1). https://doi.org/10.1111/xen.70115.
DOI: https://doi.org/10.1111/xen.70115

Interpretive Summary: There is a critical shortage of human organs for patients who need replacement organs. Many people never receive the life saving organs they need. The transplantation of pig organs to humans is becoming increasingly important to be able to save lives that are waiting for an organ transplant. Here, we present information on two pig genes that play an important role in the rejection of organs by humans and how deactivating these genes does not affect pig health. The data provided illustrates important information about the pig gene sequence and function, which can positively impact the process of creating pigs that can be used for organ transplantation into humans. Collectively, this data provides important information about the pig B4GALNT2/B4GALNT2-like genes, which can positively impact the process of creation of organs-source pigs.

Technical Abstract: The B4GALNT2 gene has become an important target for xenotransplantation because its inactivation reduces the antigenicity of porcine tissues. The growing use of organ-source pig models has led to an increased demand for the rapid creation of these animals. However, the physiological role of this gene in pigs remains poorly understood. In 2015, after generating pigs lacking B4GALNT2 expression, researchers observed a third allele for this gene. Subsequently, another gene, described as B4GALNT2-like, was found in the porcine genome. We have collected data over four years since the production of our first line of xenotransplantation pigs lacking B4GALNT2 and B4GALNT2-like expression. In this study, we were able to show that pig cells expressing B4GALNT2-like also reacted to Dolichos biflorus Agglutinin (DBA) lectin, which recognizes GalNAc epitopes. Additionally, we demonstrated that B4GALNT2/B4GALNT2-like knockout embryos were able to be carried to term in females with the same genotype. We hypothesized that the presence of both genes in the porcine genome might have occurred due to duplication, inversion, and reinsertion of part of the Phospho1-B4GALNT2 segment. Finally, the pig B4GALNT2-like gene showed greater similarity to the human, bovine, and murine B4GALNT2 genes than the original pig B4GALNT2. These data clarify the importance of targeting both B4GALNT2 and B4GALNT2-like for xenotransplantation studies and have improved our knowledge about their genomic structure and role in pig reproduction.