Generation of isogenic single and multiplex gene knockout mice by base editing-induced STOP

doi:10.1016/j.scib.2018.07.002

	Generation of isogenic single and multiplex gene knockout mice by base editing-induced STOP
	Yang, Guang1 ; Zhu, Tianyu 2; Lu, Zongyang1 ; Li, Guanglei1 ; Zhang, Hao 2; Feng, Songjie1 ; Liu, Yajing1 ; Li, Jianan1 ; Zhang, Yu1 ; Chen, Jia1 ; Guo, Xuejiang 2; Huang, Xingxu1
	2018-09-15
发表期刊	SCIENCE BULLETIN (IF:18.8[JCR-2023],15.8[5-Year])
ISSN	2095-9273
卷号	63 期号:17 页码:1101-1107
发表状态	已发表
DOI	10.1016/j.scib.2018.07.002
摘要	Although CRISPR/Cas9 has been widely used to generate knockout mice, two major limitations remain: the founders usually carry a mixture of genotypes, and mosaicism harboring multiple genotypes. Therefore, it takes a long time to get homozygous mutants. Recently developed base editing (BE) system, which introduces C-to-T conversion without double strand DNA cleavage, has been used to introduce artificial stop codons (i-STOP) to prematurely terminate translation, providing a cleaner strategy for genome engineering. Using this strategy, we generated CD160 KO and VISTA/CD160 double KO mice by microinjection of a single sgRNA targeting CD160 and a mixture of sgRNAs targeting VISTA and CD160, respectively. The BE system induced STOP efficiently in mouse embryos and consequently in founder mice without detectable off-target. Most interestingly, the majority of the mutants harbor same genetic modifications, indicating we generated isogenic single and multiplex gene mutant mice by BE-induced STOP. We also obtained homozygous mutant mouse in F1 mice, demonstrating the accelerated strategy in generating animal models. (C) 2018 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.
关键词	Base editing i-STOP Isogenic Knockout VISTA CD160
收录类别	SCI ; SCIE ; EI ; CSCD
语种	英语
资助项目	[SKLRM-K201502]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000444100500004
CSCD记录号	CSCD:6337010
出版者	SCIENCE PRESS
WOS关键词	ONE-STEP GENERATION ; MOUSE ZYGOTES ; GENOME ; CAS9 ; MUTATIONS ; EMBRYOS
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/27781
专题	生命科学与技术学院生命科学与技术学院_PI研究组_陈佳组生命科学与技术学院_PI研究组_黄行许组生命科学与技术学院_硕士生生命科学与技术学院_博士生
通讯作者	Guo, Xuejiang; Huang, Xingxu
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.Nanjing Med Univ, Dept Histol & Embryol, State Key Lab Reprod Med, Nanjing 211166, Jiangsu, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Yang, Guang,Zhu, Tianyu,Lu, Zongyang,et al. Generation of isogenic single and multiplex gene knockout mice by base editing-induced STOP[J]. SCIENCE BULLETIN,2018,63(17):1101-1107.
APA	Yang, Guang.,Zhu, Tianyu.,Lu, Zongyang.,Li, Guanglei.,Zhang, Hao.,...&Huang, Xingxu.(2018).Generation of isogenic single and multiplex gene knockout mice by base editing-induced STOP.SCIENCE BULLETIN,63(17),1101-1107.
MLA	Yang, Guang,et al."Generation of isogenic single and multiplex gene knockout mice by base editing-induced STOP".SCIENCE BULLETIN 63.17(2018):1101-1107.