Abstract
The cancer genome is highly complex, with hundreds of point mutations, translocations, and chromosome gains and losses per tumor. To understand the effects of these alterations, precise models are needed. Traditional approaches to the construction of mouse models are time-consuming and laborious, requiring manipulation of embryonic stem cells and multiple steps. The recent development of the clustered regularly interspersed short palindromic repeats (CRISPR)-Cas9 system, a powerful genome-editing tool for efficient and precise genome engineering in cultured mammalian cells and animals, is transforming mouse-model generation. Here, we review how CRISPR-Cas9 has been used to create germline and somatic mouse models with point mutations, deletions and complex chromosomal rearrangements. We highlight the progress and challenges of such approaches, and how these models can be used to understand the evolution and progression of individual tumors and identify new strategies for cancer treatment. The generation of precision cancer mouse models through genome editing will provide a rapid avenue for functional cancer genomics and pave the way for precision cancer medicine.
Highlights
The cancer genome is highly complex, with hundreds of point mutations, translocations, and chromosome gains and losses per tumor
As the field moved towards more precise genome editing, programmable nucleases, including zinc-finger nucleases (ZFNs) and transcription-activator-like effector nucleases (TALENs) [7], have been developed
It will allow researchers to explore therapeutic strategies inspired by clustered regularly interspersed short palindromic repeats (CRISPR)-based genetic screens [74]
Summary
The cancer genome is highly complex, with hundreds of point mutations, translocations, and chromosome gains and losses per tumor. In the face of such a complex genomic landscape, there is a need for simple and flexible genetic methods to generate mouse models that can identify functional cancer driver genes among the vast number of passenger mutations. Tag or a fluorescent reporter construct in Nanog, Sox2 and Oct4 (important stem cell genes) as well as a Mecp2 conditional mutation (a Rett syndrome gene) were generated by one-step co-injection of zygotes with Cas9 mRNA, different sgRNAs and DNA vectors (Fig. 3a) [18].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
