Production of Wilson Disease Model Rabbits with Homology-Directed Precision Point Mutations in the ATP7B Gene Using the CRISPR/Cas9 System

doi:10.1038/s41598-018-19774-4

	Production of Wilson Disease Model Rabbits with Homology-Directed Precision Point Mutations in the ATP7B Gene Using the CRISPR/Cas9 System
	Jiang, Weihua 1; Liu, Lili 1; Chang, Qiurong 1; Xing, Fengying 1; Ma, Zhengwen 1; Fang, Zhenfu 1; Zhou, Jing 1; Fu, Li 1; Wang, Huiyang 1; Huang, Xingxu2 ; Chen, Xuejin 1; Li, Yao 1; Li, Shangang 1
	2018-01-22
发表期刊	SCIENTIFIC REPORTS
ISSN	2045-2322
卷号	8
发表状态	已发表
DOI	10.1038/s41598-018-19774-4
摘要	CRISPR/Cas9 has recently been developed as an efficient genome engineering tool. The rabbit is a suitable animal model for studies of metabolic diseases. In this study, we generated ATP7B site-directed point mutation rabbits to simulate a major mutation type in Asians (p. Arg778Leu) with Wilson disease (WD) by using the CRISPR/Cas9 system combined with single-strand DNA oligonucleotides (ssODNs). The efficiency of the precision point mutation was 52.94% when zygotes were injected 14 hours after HCG treatment and was significantly higher than that of zygotes injected 19 hours after HCG treatment (14.29%). The rabbits carrying the allele with mutant ATP7B died at approximately three months of age. Additionally, the copper content in the livers of rabbits at the onset of WD increased nine-fold, a level similar to the five-fold increase observed in humans with WD. Thus, the efficiency of precision point mutations increases when RNAs are injected into zygotes at earlier stages, and the ATP7B mutant rabbits are a potential model for human WD disease with applications in pathological analysis, clinical treatment and gene therapy research.
收录类别	SCI ; SCIE
语种	英语
资助项目	Shanghai Natural Science Fund[15140901700]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000422912100015
出版者	NATURE PUBLISHING GROUP
WOS关键词	ZINC-FINGER NUCLEASES ; MOUSE EMBRYOS ; CONDITIONAL ALLELES ; APOLIPOPROTEIN-E ; STEP GENERATION ; KOREAN PATIENTS ; KNOCKOUT RATS ; CELLS ; IDENTIFICATION ; MICE
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/16295
专题	生命科学与技术学院_PI研究组_黄行许组
通讯作者	Li, Yao; Li, Shangang
作者单位	1.Shanghai Jiao Tong Univ, Sch Med, Dept Lab Anim Sci, Shanghai 200025, Peoples R China 2.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Jiang, Weihua,Liu, Lili,Chang, Qiurong,et al. Production of Wilson Disease Model Rabbits with Homology-Directed Precision Point Mutations in the ATP7B Gene Using the CRISPR/Cas9 System[J]. SCIENTIFIC REPORTS,2018,8.
APA	Jiang, Weihua.,Liu, Lili.,Chang, Qiurong.,Xing, Fengying.,Ma, Zhengwen.,...&Li, Shangang.(2018).Production of Wilson Disease Model Rabbits with Homology-Directed Precision Point Mutations in the ATP7B Gene Using the CRISPR/Cas9 System.SCIENTIFIC REPORTS,8.
MLA	Jiang, Weihua,et al."Production of Wilson Disease Model Rabbits with Homology-Directed Precision Point Mutations in the ATP7B Gene Using the CRISPR/Cas9 System".SCIENTIFIC REPORTS 8(2018).