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Efficient generation of B2m-null pigs via injection of zygote with TALENs | |
Wang, Yong1; Du, Yinan2,3; Zhou, Xiaoyang1; Wang, Lulu1; Li, Jian4; Wang, Fengchao5; Huang, Zhengen6; Huang, Xingxu2,3; Wei, Hong1 | |
2016-12-16 | |
发表期刊 | SCIENTIFIC REPORTS |
ISSN | 2045-2322 |
卷号 | 6 |
发表状态 | 已发表 |
DOI | 10.1038/srep38854 |
摘要 | Donor major histocompatibility complex class I (MHC I) molecules are the main targets of the host immune response after organ allotransplantation. Whether and how MHC I-deficiency of pig donor tissues affects rejection after xenotransplantation has not been assessed. Beta2-microglobulin (B2M) is indispensable for the assembly of MHC I receptors and therefore provides an effective target to disrupt cell surface MHC I expression. Here, we report the one-step generation of mutant pigs with targeted disruptions in B2m by injection of porcine zygotes with B2m exon 2-specific TALENs. After germline transmission of mutant B2m alleles, we obtained F1 pigs with biallelic B2m frameshift mutations. F1 pigs lacked detectable B2M expression in tissues derived from the three germ layers, and their lymphocytes were devoid of MHC I surface receptors. Skin grafts from B2M deficient pigs exhibited remarkably prolonged survival on xenogeneic wounds compared to tissues of non-mutant littermates. Mutant founder pigs with bi-allelic disruption in B2m and B2M deficient F1 offspring did not display visible abnormalities, suggesting that pigs are tolerant to B2M deficiency. In summary, we show the efficient generation of pigs with germline mutations in B2m, and demonstrate a beneficial effect of donor MHC I-deficiency on xenotransplantation. |
收录类别 | SCI |
语种 | 英语 |
资助项目 | National Natural Science Foundation of China[31171377] ; National Natural Science Foundation of China[31171280] ; National Natural Science Foundation of China[31201081] |
WOS研究方向 | Science & Technology - Other Topics |
WOS类目 | Multidisciplinary Sciences |
WOS记录号 | WOS:000389874600001 |
出版者 | NATURE PUBLISHING GROUP |
WOS关键词 | DECAY-ACCELERATING FACTOR ; NATURAL-KILLER-CELLS ; TRANSGENIC EXPRESSION ; HUMAN-COMPLEMENT ; GENE KNOCKOUT ; PROTECTION ; MICE ; XENOGRAFTS ; REJECTION ; LIVESTOCK |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1599 |
专题 | 生命科学与技术学院_PI研究组_黄行许组 |
通讯作者 | Huang, Xingxu; Wei, Hong |
作者单位 | 1.Third Mil Med Univ, Coll Basic Med Sci, Dept Lab Anim Sci, Chongqing 400038, Peoples R China 2.Nanjing Univ, Natl Resource Ctr Mutant Mice, Model Anim Res Ctr, MOE Key Lab Model Anim Dis Study, Nanjing 210061, Jiangsu, Peoples R China 3.ShanghaiTech Univ, Pudong New Area, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China 4.Third Mil Med Univ, Dept Immunol, Coll Basic Med Sci, Chongqing 400038, Peoples R China 5.Third Mil Med Univ, Coll Mil Prevent Med, Inst Combined Injury, Chongqing 400038, Peoples R China 6.Third Mil Med Univ, Southwest Hosp, Res Inst Burns, Chongqing 400038, Peoples R China |
通讯作者单位 | 生命科学与技术学院 |
推荐引用方式 GB/T 7714 | Wang, Yong,Du, Yinan,Zhou, Xiaoyang,et al. Efficient generation of B2m-null pigs via injection of zygote with TALENs[J]. SCIENTIFIC REPORTS,2016,6. |
APA | Wang, Yong.,Du, Yinan.,Zhou, Xiaoyang.,Wang, Lulu.,Li, Jian.,...&Wei, Hong.(2016).Efficient generation of B2m-null pigs via injection of zygote with TALENs.SCIENTIFIC REPORTS,6. |
MLA | Wang, Yong,et al."Efficient generation of B2m-null pigs via injection of zygote with TALENs".SCIENTIFIC REPORTS 6(2016). |
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