Simultaneous zygotic inactivation of multiple genes in mouse through CRISPR/Cas9-mediated base editing
文献类型：期刊论文
| 作者 | Zhang, He2,3; Pan, Hong2; Zhou, Changyang2,3; Wei, Yu2; Ying, Wenqin2; Li, Shuting2; Wang, Guangqin2; Li, Chao2; Ren, Yifei2,3; Yang, Hui2 |
| 刊名 | DEVELOPMENT
 |
| 出版日期 | 2018 |
| 卷号 | 145期号:20页码:UNSP dev168906 |
| 关键词 | Inner ear vGlut3 Prestin Otoferlin Base editing CRISPR/Cas9 |
| ISSN号 | 0950-1991 |
| DOI | 10.1242/dev.168906 |
| 文献子类 | Article |
| 英文摘要 | In vivo genetic mutation has become a powerful tool for dissecting gene function; however, multi-gene interaction and the compensatory mechanisms involved can make findings from single mutations, at best difficult to interpret, and, at worst, misleading. Hence, it is necessary to establish an efficient way to disrupt multiple genes simultaneously. CRISPR/Cas9-mediated base editing disrupts gene function by converting a protein-coding sequence into a stop codon; this is referred to as CRISPR-stop. Its application in generating zygotic mutations has not been well explored yet. Here, we first performed a proof-of-principle test by disrupting Atoh1, a gene crucial for auditory hair cell generation. Next, we individually mutated vGlut3 (Slc17a8), otoferlin (Otof) and prestin (Slc26a5), three genes needed for normal hearing function. Finally, we successfully disrupted vGlut3, Otof and prestin simultaneously. Our results show that CRISPR-stop can efficiently generate single or triple homozygous F0 mouse mutants, bypassing laborious mouse breeding. We believe that CRISPR-stop is a powerful method that will pave the way for high-throughput screening of mouse developmental and functional genes, matching the efficiency of methods available for model organisms such as Drosophila. |
| 学科主题 | Developmental Biology |
| WOS关键词 | OUTER HAIR-CELLS ; VESICULAR GLUTAMATE TRANSPORTER-3 ; HEARING-LOSS ; IN-VIVO ; MAMMALIAN COCHLEA ; MOTOR PROTEIN ; INNER-EAR ; PRESTIN ; GENOME ; DEAFNESS |
| 语种 | 英语 |
| WOS记录号 | WOS:000449152600010 |
| 出版者 | COMPANY BIOLOGISTS LTD |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/866]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Fudan Univ, Collaborat Innovat Ctr Genet & Dev, Shanghai 200032, Peoples R China; 2.Chinese Acad Sci, CAS Ctr Excellence Bra Sci & Intelligence Technol, Inst Neurosci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China; 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 4.Guangxi Univ, Nanning 530004, Guangxi, Peoples R China; 5.Shanghai Jiao Tong Univ, Peoples Hosp 9, Sch Med, Dept Otolaryngol Head & Neck Surg, Shanghai 200011, Peoples R China; 6.Shanghai Jiao Tong Univ, Ear Inst, Sch Med, Shanghai 200011, Peoples R China; 7.Shanghai Key Lab Translat Med Ear & Nose Dis, Shanghai 200011, Peoples R China; 8.Univ Massachusetts, Biol Dept, Amherst, MA 01003 USA; 9.Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Key Lab Computat Biol, Shanghai 200031, Peoples R China; 10.Shanghai Ind Technol Inst, Shanghai Ctr Bioinformat Technol, Shanghai 200032, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Zhang, He,Pan, Hong,Zhou, Changyang,et al. Simultaneous zygotic inactivation of multiple genes in mouse through CRISPR/Cas9-mediated base editing[J]. DEVELOPMENT,2018,145(20):UNSP dev168906. |
| APA | Zhang, He.,Pan, Hong.,Zhou, Changyang.,Wei, Yu.,Ying, Wenqin.,...&,.(2018).Simultaneous zygotic inactivation of multiple genes in mouse through CRISPR/Cas9-mediated base editing.DEVELOPMENT,145(20),UNSP dev168906. |
| MLA | Zhang, He,et al."Simultaneous zygotic inactivation of multiple genes in mouse through CRISPR/Cas9-mediated base editing".DEVELOPMENT 145.20(2018):UNSP dev168906. |
入库方式： OAI收割
来源：上海营养与健康研究所
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