Efficient generation of B2m-null pigs via injection of zygote with TALENs

• DOI: 10.1038/srep38854
• Publication Date: 2016-12-17T07:12:19Z
• Authors: Yong Wang; Yinan Du; Xiaoyang Zhou; Lulu Wang; Jian Li; Fengchao Wang; Zhengen Huang; Xingxu Huang; Hong Wei
• Keywords: Xenotransplantation; Beta-2 microglobulin; Neonatal Fc receptor; Allotransplantation

Abstract Donor major histocompatibility complex class I (MHC I) molecules are the main targets of host immune response after organ allotransplantation. Whether and how MHC I-deficiency pig donor tissues affects rejection xenotransplantation has not been assessed. Beta2-microglobulin (B2M) is indispensable for assembly receptors therefore provides an effective target to disrupt cell surface expression. Here, we report one-step generation mutant pigs with targeted disruptions in B2m by injection porcine zygotes exon 2-specific TALENs. After germline transmission alleles, obtained F1 biallelic frameshift mutations. lacked detectable B2M expression derived from three germ layers, their lymphocytes were devoid receptors. Skin grafts deficient exhibited remarkably prolonged survival on xenogeneic wounds compared non-mutant littermates. Mutant founder bi-allelic disruption offspring did display visible abnormalities, suggesting that tolerant deficiency. In summary, show efficient mutations , demonstrate a beneficial effect xenotransplantation.