In:
Genome Research, Cold Spring Harbor Laboratory, Vol. 27, No. 12 ( 2017-12), p. 2061-2071
Abstract:
Despite being time-consuming and costly, generating genome-edited pigs holds great promise for agricultural, biomedical, and pharmaceutical applications. To further facilitate genome editing in pigs, we report here establishment of a pig line with Cre-inducible Cas9 expression that allows a variety of ex vivo genome editing in fibroblast cells including single- and multigene modifications, chromosome rearrangements, and efficient in vivo genetic modifications. As a proof of principle, we were able to simultaneously inactivate five tumor suppressor genes ( TP53 , PTEN , APC , BRCA1 , and BRCA2 ) and activate one oncogene ( KRAS ), achieved by delivering Cre recombinase and sgRNAs, which caused rapid lung tumor development. The efficient genome editing shown here demonstrates that these pigs can serve as a powerful tool for dissecting in vivo gene functions and biological processes in a temporal manner and for streamlining the production of genome-edited pigs for disease modeling.
Type of Medium:
Online Resource
ISSN:
1088-9051
,
1549-5469
DOI:
10.1101/gr.222521.117
Language:
English
Publisher:
Cold Spring Harbor Laboratory
Publication Date:
2017
detail.hit.zdb_id:
1483456-X
SSG:
12
