Generation of knockout mouse models of cyclin-dependent kinase inhibitors by engineered nuclease-mediated genome editing / 한국실험동물학회지
Laboratory Animal Research
; : 264-269, 2018.
Article
in En
| WPRIM
| ID: wpr-718841
Responsible library:
WPRO
ABSTRACT
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.
Key words
Full text:
1
Database:
WPRIM
Main subject:
Phosphotransferases
/
Sarcoma
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DNA
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Cell Cycle
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Exons
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G1 Phase
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Mutagenesis, Insertional
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Reading Frames
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Genome
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Mice, Knockout
Limits:
Animals
Language:
En
Journal:
Laboratory Animal Research
Year:
2018
Document type:
Article