Generation and comparison of CRISPR-Cas9 and Cre-mediated genetically engineered mouse models of sarcoma.
Generation and comparison of CRISPR-Cas9 and Cre-mediated genetically engineered mouse models of sarcoma.
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DOI：
10.1038/ncomms15999
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发表时间：
2017-07-10
影响因子：
16.6
通讯作者：
Kirsch DG
中科院分区：
文献类型：
--
作者：
Huang J;Chen M;Whitley MJ;Kuo HC;Xu ES;Walens A;Mowery YM;Van Mater D;Eward WC;Cardona DM;Luo L;Ma Y;Lopez OM;Nelson CE;Robinson-Hamm JN;Reddy A;Dave SS;Gersbach CA;Dodd RD;Kirsch DG
采用位点特异性重组酶技术的基因工程小鼠模型是癌症研究的重要工具，但可能昂贵且耗时。CRISPR-Cas9系统已经被改造成可以在小鼠体内产生自体肿瘤，但这些肿瘤与传统重组酶技术产生的肿瘤相比如何，仍有待充分探索。在这里，我们使用CRISPR-Cas9在野生型和基因工程小鼠中有效地产生原发性肉瘤的多种亚型。这些数据表明，CRISPR-Cas9可用于在小鼠中产生多种亚型的软组织肉瘤。用CRISPR-Cas9和Cre重组酶技术产生的原发性肉瘤具有相似的组织学、生长动力学、拷贝数变异和突变负荷，如通过全外显子组测序评估的。这些结果表明，用CRISPR-Cas9技术产生的肉瘤与用常规建模技术产生的肉瘤相似，并表明CRISPR-Cas9可用于更快速地产生基因型和表型相似的癌症。位点特异性重组和CRISPR-Cas9已用于产生癌症的基因工程小鼠模型。在这里，作者比较了使用两种系统生成的肉瘤，并看到了相似的遗传和细胞表型，这表明CRISPR-Cas9可用于快速生成肉瘤模型。
Genetically engineered mouse models that employ site-specific recombinase technology are important tools for cancer research but can be costly and time-consuming. The CRISPR-Cas9 system has been adapted to generate autochthonous tumours in mice, but how these tumours compare to tumours generated by conventional recombinase technology remains to be fully explored. Here we use CRISPR-Cas9 to generate multiple subtypes of primary sarcomas efficiently in wild type and genetically engineered mice. These data demonstrate that CRISPR-Cas9 can be used to generate multiple subtypes of soft tissue sarcomas in mice. Primary sarcomas generated with CRISPR-Cas9 and Cre recombinase technology had similar histology, growth kinetics, copy number variation and mutational load as assessed by whole exome sequencing. These results show that sarcomas generated with CRISPR-Cas9 technology are similar to sarcomas generated with conventional modelling techniques and suggest that CRISPR-Cas9 can be used to more rapidly generate genotypically and phenotypically similar cancers. Site-specific recombination and CRISPR-Cas9 have been used to generate genetically engineered mouse models of cancer. Here the authors compare sarcomas generated using both systems and see similar genetic and cellular phenotypes, suggesting CRISPR-Cas9 can be used to rapidly generate sarcoma models.
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影响因子：
7
作者：
Cho SW;Kim S;Kim Y;Kweon J;Kim HS;Bae S;Kim JS
通讯作者：
Kim JS
影响因子：
46.9
作者：
Heck, Dirk;Kowalczyk, Monika S.;Yudovich, David;Belizaire, Roger;Puram, Rishi V.;McConkey, Marie E.;Thielke, Anne;Aster, Jon C.;Regev, Aviv;Ebert, Benjamin L.
通讯作者：
Ebert, Benjamin L.
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
56.9
作者：
Jinek, Martin;Chylinski, Krzysztof;Charpentier, Emmanuelle
通讯作者：
Charpentier, Emmanuelle
DOI：
10.1073/pnas.88.15.6427
发表时间：
1991-08-01
影响因子：
11.1
作者：
LEVINE, DS;SANCHEZ, CA;REID, BJ
通讯作者：
REID, BJ