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Generation and comparison of CRISPR-Cas9 and Cre-mediated genetically engineered mouse models of sarcoma

Jianguo Huang, Mark Chen, Melodi Javid Whitley, Hsuan-Cheng Kuo, Eric S. Xu, Andrea Walens, Yvonne M. Mowery, David Van Mater, William C. Eward, Diana M. Cardona, Lixia Luo, Yan Ma, Omar M. Lopez, Christopher E. Nelson, Jacqueline N. Robinson-Hamm, Anupama Reddy, Sandeep S. Dave, Charles A. Gersbach, Rebecca D. Dodd and David G. Kirsch ()
Additional contact information
Jianguo Huang: Duke University Medical Center
Mark Chen: Duke University Medical Center
Melodi Javid Whitley: Duke University Medical Center
Hsuan-Cheng Kuo: Duke University Medical Center
Eric S. Xu: Duke University Medical Center
Andrea Walens: Duke University Medical Center
Yvonne M. Mowery: Duke University Medical Center
David Van Mater: Duke University Medical Center
William C. Eward: Duke University
Diana M. Cardona: Duke University
Lixia Luo: Duke University Medical Center
Yan Ma: Duke University Medical Center
Omar M. Lopez: Duke University Medical Center
Christopher E. Nelson: Duke University
Jacqueline N. Robinson-Hamm: Duke University
Anupama Reddy: Duke Center for Genomic and Computational Biology, Duke University
Sandeep S. Dave: Duke Center for Genomic and Computational Biology, Duke University
Charles A. Gersbach: Duke University
Rebecca D. Dodd: Duke University Medical Center
David G. Kirsch: Duke University Medical Center

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract 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.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15999

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DOI: 10.1038/ncomms15999

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