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
ISSN2045-2322
卷号6
发表状态已发表
DOI10.1038/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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