CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling

Platt, Randall J.; Chen, Sidi; Zhou, Yang; Yim, Michael J.; Swiech, Lukasz; Kempton, Hannah R.; Dahlman, James E.; Parnas, Oren; Eisenhaure, Thomas M.; Jovanovic, Marko; Graham, Daniel B.; Jhunjhunwala, Siddharth; Xavier, Ramnik J.; Langer, Robert; Anderson, Daniel G.; Hacohen, Nir; Regev, Aviv; Feng, Guoping; Sharp, Phillip A.; Zhang, Feng

doi:10.1016/j.cell.2014.09.014

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CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling

Published Date:

Sep 25 2014

Publisher's site:

http://dx.doi.org/10.1016/j.cell.2014.09.014 New Site Icon

Source:

Cell. 2014; 159(2):440-455.

[PDF-3.28 MB]

Details:

Personal Authors:

Platt, Randall J. ; Chen, Sidi ; Zhou, Yang ; Yim, Michael J. ; Swiech, Lukasz ; ... More ▼

Keywords:

[+]

Pubmed ID:

25263330

Pubmed Central ID:

PMC4265475

Description:

CRISPR-Cas9 is a versatile genome editing technology for studying the functions of genetic elements. To broadly enable the application of Cas9 in vivo, we established a Cre-dependent Cas9 knockin mouse. We demonstrated in vivo as well as ex vivo genome editing using adeno-associated virus (AAV)-, lentivirus-, or particle-mediated delivery of guide RNA in neurons, immune cells, and endothelial cells. Using these mice, we simultaneously modeled the dynamics of KRAS, p53, and LKB1, the top three significantly mutated genes in lung adenocarcinoma. Delivery of a single AAV vector in the lung generated loss-of-function mutations in p53 and Lkb1, as well as homology-directed repair-mediated Kras(G12D) mutations, leading to macroscopic tumors of adenocarcinoma pathology. Together, these results suggest that Cas9 mice empower a wide range of biological and disease modeling applications.

Document Type:

Journal Article

Collection(s):

CDC Public Access

Funding:

Supporting Files:

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