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; David G Kirsch

doi:10.1038/ncomms15999

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

Journal article

Open access

Peer reviewed

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, …

Nature communications, Vol.8(1), pp.15999-15999

07/10/2017

DOI: 10.1038/ncomms15999

PMCID: PMC5508130

PMID: 28691711

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https://doi.org/10.1038/ncomms15999View

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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.

Animals

CRISPR-Cas Systems

Electroporation

Gene Editing - methods

Integrases

Male

Mice

Mice, Nude

Mutation

Neurilemmoma - genetics

Neurilemmoma - pathology

NIH 3T3 Cells

Sarcoma, Experimental - genetics

Sarcoma, Experimental - pathology

Details

Title: Subtitle: Generation and comparison of CRISPR-Cas9 and Cre-mediated genetically engineered mouse models of sarcoma
Creators: Jianguo Huang - Duke University
Mark Chen - Duke University
Melodi Javid Whitley - Duke University
Hsuan-Cheng Kuo - Duke University
Eric S Xu - Duke University
Andrea Walens - Duke University
Yvonne M Mowery - Duke University
David Van Mater - Duke University
William C Eward - Duke University
Diana M Cardona - Duke University
Lixia Luo - Duke University
Yan Ma - Duke University
Omar M Lopez - Duke University
Christopher E Nelson - Duke University
Jacqueline N Robinson-Hamm - Duke University
Anupama Reddy - Duke University
Sandeep S Dave - Duke University
Charles A Gersbach - Duke University
Rebecca D Dodd - Duke University
David G Kirsch - Duke University
Resource Type: Journal article
Publication Details: Nature communications, Vol.8(1), pp.15999-15999
DOI: 10.1038/ncomms15999
PMID: 28691711
PMCID: PMC5508130
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Grant note: F30 CA206424 / NCI NIH HHS T32 GM007171 / NIGMS NIH HHS P30 CA086862 / NCI NIH HHS R35 CA197616 / NCI NIH HHS
Language: English
Date published: 07/10/2017
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984359867402771

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