Analysis of microsatellite instability in CRISPR/Cas9 editing mice
Analysis of microsatellite instability in CRISPR/Cas9 editing mice
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CRISPR/Cas9 编辑小鼠的微卫星不稳定性分析
DOI：
10.1016/j.mrfmmm.2017.02.003
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发表时间：
2017-03-01
影响因子：
2.3
通讯作者：
Du, Xiaoyan
中科院分区：
文献类型：
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作者：
Huo, Xueyun;Du, Yating;Du, Xiaoyan
规则间隔短回文重复序列（CRISPR）/CRISPR相关蛋白（Cas）9系统是一种新型的、功能强大的基因组编辑工具。CRISPR/Cas9是RNA引导的，可以导致所需的基因组修饰。然而，CRISPR/Cas9介导的基因组编辑是否会导致基因组改变和基因组不稳定性，如微卫星不稳定性（MSI），仍然是未知的。在这里，我们使用从我们以前的研究中选择的42个微卫星位点的面板检测了21个CRISPR/Cas9小鼠品系中的MSI。令人惊讶的是，MSI发生在CRISPR/Cas9修饰的基因组中是常见的，并且大多数检查的菌株（19/21，90.5%）显示MSI。在检测的42个基因座中，8个基因座（8/42，19.05%）在Cas9编辑小鼠中表现出MSI。在我们测试的Cas9菌株中，Ttll 9（4/42，9.5%）是最不稳定的菌株，并且D10 Mit 3和D10 Mit 198（9/21，42.9%）被认为是最“热”的基因座。通过分析微卫星位点的突变，我们对CRISPR/Cas9模型的基因组改变提供了新的见解，这将有助于我们更好地理解这项强大的技术。(C)2017爱思唯尔B. V.保留所有权利。
Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR- associated (Cas) protein 9 system is a novel and powerful tool which is widely used for genome editing. CRISPR/Cas9 is RNA-guided and can lead to desired genomic modifications. However, whether the CRISPR/Cas9-mediated genome editing causes genomic alterations and genomic instability, such as microsatellite instability (MSI), is still unknown. Here we detected MSI in 21 CRISPR/Cas9 mouse strains using a panel of 42 microsatellite loci which were selected from our previous studies. Surprisingly, MSI occurrence was common in CRISPR/Cas9 modified genome, and most of the strains (19/21, 90.5%) examined showed MSI. Of 42 loci examined, 8 loci (8/42, 19.05%) exhibited MSI in the Cas9 editing mice. The Ttll9 (4/42, 9.5%) were the most unstable strains, and D10Mit3 and D10Mit198 (9/21, 42.9%) were considered to be the most "hot" loci in the Cas9 strains we tested. Through analyzing the mutation of microsatellite loci, we provide new insights into the genomic alterations of CRISPR/Cas9 models and it will help us for a better understanding of this powerful technology. (C) 2017 Elsevier B.V. All rights reserved.