High-efficiency and heritable gene targeting in mouse by transcription activator-like effector nucleases
文献类型:期刊论文
作者 | Qiu, Zhongwei3,4; Liu, Meizhen3,4; Chen, Zhaohua3,4; Shao, Yanjiao3,4; Pan, Hongjie3,4; Wei, Gaigai3,4; Yu, Chao5; Zhang, Long3,4; Li, Xia3,4; Wang, Ping3,4 |
刊名 | NUCLEIC ACIDS RESEARCH
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出版日期 | 2013-06 |
卷号 | 41期号:11 |
ISSN号 | 0305-1048 |
DOI | 10.1093/nar/gkt258 |
文献子类 | Article |
英文摘要 | Transcription activator-like effector nucleases (TALENs) are a powerful new approach for targeted gene disruption in various animal models, but little is known about their activities in Mus musculus, the widely used mammalian model organism. Here, we report that direct injection of in vitro transcribed messenger RNA of TALEN pairs into mouse zygotes induced somatic mutations, which were stably passed to the next generation through germ-line transmission. With one TALEN pair constructed for each of 10 target genes, mutant F0 mice for each gene were obtained with the mutation rate ranged from 13 to 67% and an average of similar to 40% of total healthy newborns with no significant differences between C57BL/6 and FVB/N genetic background. One TALEN pair with single mismatch to their intended target sequence in each side failed to yield any mutation. Furthermore, highly efficient germ-line transmission was obtained, as all the F0 founders tested transmitted the mutations to F1 mice. In addition, we also observed that one bi-allele mutant founder of Lepr gene, encoding Leptin receptor, had similar diabetic phenotype as db/db mouse. Together, our results suggest that TALENs are an effective genetic tool for rapid gene disruption with high efficiency and heritability in mouse with distinct genetic background. |
WOS关键词 | ZINC-FINGER NUCLEASES ; STEM-CELLS ; TAL EFFECTORS ; EMBRYO MICROINJECTION ; GENOME MODIFICATION ; CLEAVAGE DOMAIN ; KNOCKOUT RATS ; DNA-CLEAVAGE ; DISRUPTION ; ZEBRAFISH |
资助项目 | State Key Development Programs of China[2012CB910400] ; State Key Development Programs of China[2010CB945403] ; National Natural Science Foundation of China[31171318] ; National Natural Science Foundation of China[30930055] ; Science and Technology Commission of Shanghai Municipality[11DZ2260300] |
WOS研究方向 | Biochemistry & Molecular Biology |
语种 | 英语 |
WOS记录号 | WOS:000320116200009 |
出版者 | OXFORD UNIV PRESS |
源URL | [http://119.78.100.183/handle/2S10ELR8/277601] ![]() |
专题 | 中国科学院上海药物研究所 |
通讯作者 | Li, Dali |
作者单位 | 1.Texas A&M Univ, Hlth Sci Ctr, Inst Biosci & Technol, Houston, TX 77030 USA 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.E China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai 200241, Peoples R China; 4.E China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China; 5.Zhejiang Univ, Inst Life Sci, Hangzhou 310058, Zhejiang, Peoples R China; |
推荐引用方式 GB/T 7714 | Qiu, Zhongwei,Liu, Meizhen,Chen, Zhaohua,et al. High-efficiency and heritable gene targeting in mouse by transcription activator-like effector nucleases[J]. NUCLEIC ACIDS RESEARCH,2013,41(11). |
APA | Qiu, Zhongwei.,Liu, Meizhen.,Chen, Zhaohua.,Shao, Yanjiao.,Pan, Hongjie.,...&Li, Dali.(2013).High-efficiency and heritable gene targeting in mouse by transcription activator-like effector nucleases.NUCLEIC ACIDS RESEARCH,41(11). |
MLA | Qiu, Zhongwei,et al."High-efficiency and heritable gene targeting in mouse by transcription activator-like effector nucleases".NUCLEIC ACIDS RESEARCH 41.11(2013). |
入库方式: OAI收割
来源:上海药物研究所
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