| First Author | Park BM | Year | 2018 |
| Journal | Lab Anim Res | Volume | 34 |
| Issue | 4 | Pages | 264-269 |
| PubMed ID | 30671114 | Mgi Jnum | J:281699 |
| Mgi Id | MGI:6363769 | Doi | 10.5625/lar.2018.34.4.264 |
| Citation | Park BM, et al. (2018) Generation of knockout mouse models of cyclin-dependent kinase inhibitors by engineered nuclease-mediated genome editing. Lab Anim Res 34(4):264-269 |
| abstractText | Cell cycle dysfunction can cause severe diseases, including neurodegenerative disease and cancer. Mutations in cyclin-dependent kinase inhibitors controlling the G1 phase of the cell cycle are prevalent in various cancers. Mice lacking the tumor suppressors p16(Ink4a) (Cdkn2a, cyclin-dependent kinase inhibitor 2a), p19(Arf) (an alternative reading frame product of Cdkn2a,), and p27(Kip1) (Cdkn1b, cyclin-dependent kinase inhibitor 1b) result in malignant progression of epithelial cancers, sarcomas, and melanomas, respectively. Here, we generated knockout mouse models for each of these three cyclin-dependent kinase inhibitors using engineered nucleases. The p16(Ink4a) and p19(Arf) knockout mice were generated via transcription activator-like effector nucleases (TALENs), and p27(Kip1) knockout mice via clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9). These gene editing technologies were targeted to the first exon of each gene, to induce frameshifts producing premature termination codons. Unlike preexisting embryonic stem cell-based knockout mice, our mouse models are free from selectable markers or other external gene insertions, permitting more precise study of cell cycle-related diseases without confounding influences of foreign DNA. |
