南方医科大学学报2018，Vol.38Issue(6)：639-646,8.DOI:10.3969/j.issn.1673-4254.2018.06.01
利用CRISPR/Cas9技术建立NOD/SCID/IL2Rγ-/-免疫缺陷小鼠
Generation of a new strain of NOD/SCID/IL2Rγ-/-mice with targeted disruption of Prkdc and IL2Rγ genes using CRISPR/Cas9 system
摘要
Abstract
Objective The NOD/SCID/IL2Rγ-/-(NSG) mouse strain is the most widely used immunodeficient strain for xenograft transplantation.However,the existing SCID mutation is a spontaneous mutation of the Prkdc gene,which leads to leaky T cell developmental block and difficulty in genotyping.It is therefore important to develop a new strain of NSG mice with targeted disruption of Prkdc and IL2Rγ genes.Methods Targeted disruption of Prkdc and IL2Rγ genes was achieved using the CRISPR/Cas9 system.By intercrossing the knockout and NOD mice,we obtained a novel strain of NOD/SCID/IL2Rγ-/-(NSG) mice,denoted as cNSG (Chinese NSG) mice.Results In addition to the NOD mutation,cNSG mice exhibited a complete absence of T cells,B cells and NK cells.cNSG mice allowed more efficient engraftment of human cancer cells than the commonly used immunodeficient nude mice.Conclusion cNSG mice will provide an important xenotransplantation model for biomedical research.关键词
基因工程/CRISPR/Cas9系统/免疫缺陷小鼠/cNSG品系/移植Key words
gene editing/CRISPR/Cas9 system/immunodeficiency/cNSG strain/xenotransplantation引用本文复制引用
刘亚宸,陈渠,杨兴龙,汤清双,姚开泰,徐洋..利用CRISPR/Cas9技术建立NOD/SCID/IL2Rγ-/-免疫缺陷小鼠[J].南方医科大学学报,2018,38(6):639-646,8.基金项目
国家自然科学基金(81430032,U1601222) （81430032,U1601222）
广东省肿瘤免疫治疗研究重点实验室,广州市肿瘤免疫研究重点实验室,广东省前沿与关键技术创新专项资金(2015B020225004) （2015B020225004）
广东省NSF重大培育项目.Supported by Key Research Projects of National Natural Science Foundation of China (81430032,U1601222) and by Special Funds for Frontier and Key Technology Innovation of Guangdong Province (2015B020225004) Major Basic Research Development Project of Natural Science Foundation of Guangdong Province. （81430032,U1601222）
