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Efficient generation of B2m-null pigs via injection of zygote with TALENs
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 ind...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159787/ https://www.ncbi.nlm.nih.gov/pubmed/27982048 http://dx.doi.org/10.1038/srep38854 |
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author | Wang, Yong Du, Yinan Zhou, Xiaoyang Wang, Lulu Li, Jian Wang, Fengchao Huang, Zhengen Huang, Xingxu Wei, Hong |
author_facet | Wang, Yong Du, Yinan Zhou, Xiaoyang Wang, Lulu Li, Jian Wang, Fengchao Huang, Zhengen Huang, Xingxu Wei, Hong |
author_sort | Wang, Yong |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5159787 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51597872016-12-21 Efficient generation of B2m-null pigs via injection of zygote with TALENs Wang, Yong Du, Yinan Zhou, Xiaoyang Wang, Lulu Li, Jian Wang, Fengchao Huang, Zhengen Huang, Xingxu Wei, Hong Sci Rep Article 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. Nature Publishing Group 2016-12-16 /pmc/articles/PMC5159787/ /pubmed/27982048 http://dx.doi.org/10.1038/srep38854 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Wang, Yong Du, Yinan Zhou, Xiaoyang Wang, Lulu Li, Jian Wang, Fengchao Huang, Zhengen Huang, Xingxu Wei, Hong Efficient generation of B2m-null pigs via injection of zygote with TALENs |
title | Efficient generation of B2m-null pigs via injection of zygote with TALENs |
title_full | Efficient generation of B2m-null pigs via injection of zygote with TALENs |
title_fullStr | Efficient generation of B2m-null pigs via injection of zygote with TALENs |
title_full_unstemmed | Efficient generation of B2m-null pigs via injection of zygote with TALENs |
title_short | Efficient generation of B2m-null pigs via injection of zygote with TALENs |
title_sort | efficient generation of b2m-null pigs via injection of zygote with talens |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159787/ https://www.ncbi.nlm.nih.gov/pubmed/27982048 http://dx.doi.org/10.1038/srep38854 |
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