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Rapid generation of gene-targeted EPS-derived mouse models through tetraploid complementation

One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem (ES) cells, which is used to produce gene-targeted mice for wide applications in biomedicine. However, a major bottleneck in this approach is that the robustness of germline transmission of gen...

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Autores principales: Li, Haibo, Zhao, Chaoran, Xu, Jun, Xu, Yaxing, Cheng, Chunmei, Liu, Yinan, Wang, Ting, Du, Yaqin, Xie, Liangfu, Zhao, Jingru, Han, Yanchuang, Wang, Xiaobao, Bai, Yun, Deng, Hongkui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Higher Education Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321812/
https://www.ncbi.nlm.nih.gov/pubmed/29948855
http://dx.doi.org/10.1007/s13238-018-0556-1
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author Li, Haibo
Zhao, Chaoran
Xu, Jun
Xu, Yaxing
Cheng, Chunmei
Liu, Yinan
Wang, Ting
Du, Yaqin
Xie, Liangfu
Zhao, Jingru
Han, Yanchuang
Wang, Xiaobao
Bai, Yun
Deng, Hongkui
author_facet Li, Haibo
Zhao, Chaoran
Xu, Jun
Xu, Yaxing
Cheng, Chunmei
Liu, Yinan
Wang, Ting
Du, Yaqin
Xie, Liangfu
Zhao, Jingru
Han, Yanchuang
Wang, Xiaobao
Bai, Yun
Deng, Hongkui
author_sort Li, Haibo
collection PubMed
description One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem (ES) cells, which is used to produce gene-targeted mice for wide applications in biomedicine. However, a major bottleneck in this approach is that the robustness of germline transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing, which impairs the efficiency and robustness of mouse model generation. Recently, we have established a new type of pluripotent cells termed extended pluripotent stem (EPS) cells, which have superior developmental potency and robust germline competence compared to conventional mouse ES cells. In this study, we demonstrate that mouse EPS cells well maintain developmental potency and genetic stability after long-term passage. Based on gene targeting in mouse EPS cells, we established a new approach to directly and rapidly generate gene-targeted mouse models through tetraploid complementation, which could be accomplished in approximately 2 months. Importantly, using this approach, we successfully constructed mouse models in which the human interleukin 3 (IL3) or interleukin 6 (IL6) gene was knocked into its corresponding locus in the mouse genome. Our study demonstrates the feasibility of using mouse EPS cells to rapidly generate mouse models by gene targeting, which have great application potential in biomedical research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13238-018-0556-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-63218122019-01-22 Rapid generation of gene-targeted EPS-derived mouse models through tetraploid complementation Li, Haibo Zhao, Chaoran Xu, Jun Xu, Yaxing Cheng, Chunmei Liu, Yinan Wang, Ting Du, Yaqin Xie, Liangfu Zhao, Jingru Han, Yanchuang Wang, Xiaobao Bai, Yun Deng, Hongkui Protein Cell Short Article One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem (ES) cells, which is used to produce gene-targeted mice for wide applications in biomedicine. However, a major bottleneck in this approach is that the robustness of germline transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing, which impairs the efficiency and robustness of mouse model generation. Recently, we have established a new type of pluripotent cells termed extended pluripotent stem (EPS) cells, which have superior developmental potency and robust germline competence compared to conventional mouse ES cells. In this study, we demonstrate that mouse EPS cells well maintain developmental potency and genetic stability after long-term passage. Based on gene targeting in mouse EPS cells, we established a new approach to directly and rapidly generate gene-targeted mouse models through tetraploid complementation, which could be accomplished in approximately 2 months. Importantly, using this approach, we successfully constructed mouse models in which the human interleukin 3 (IL3) or interleukin 6 (IL6) gene was knocked into its corresponding locus in the mouse genome. Our study demonstrates the feasibility of using mouse EPS cells to rapidly generate mouse models by gene targeting, which have great application potential in biomedical research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13238-018-0556-1) contains supplementary material, which is available to authorized users. Higher Education Press 2018-06-13 2019-01 /pmc/articles/PMC6321812/ /pubmed/29948855 http://dx.doi.org/10.1007/s13238-018-0556-1 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Short Article
Li, Haibo
Zhao, Chaoran
Xu, Jun
Xu, Yaxing
Cheng, Chunmei
Liu, Yinan
Wang, Ting
Du, Yaqin
Xie, Liangfu
Zhao, Jingru
Han, Yanchuang
Wang, Xiaobao
Bai, Yun
Deng, Hongkui
Rapid generation of gene-targeted EPS-derived mouse models through tetraploid complementation
title Rapid generation of gene-targeted EPS-derived mouse models through tetraploid complementation
title_full Rapid generation of gene-targeted EPS-derived mouse models through tetraploid complementation
title_fullStr Rapid generation of gene-targeted EPS-derived mouse models through tetraploid complementation
title_full_unstemmed Rapid generation of gene-targeted EPS-derived mouse models through tetraploid complementation
title_short Rapid generation of gene-targeted EPS-derived mouse models through tetraploid complementation
title_sort rapid generation of gene-targeted eps-derived mouse models through tetraploid complementation
topic Short Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321812/
https://www.ncbi.nlm.nih.gov/pubmed/29948855
http://dx.doi.org/10.1007/s13238-018-0556-1
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