Generation of knockout mouse models of cyclin-dependent kinase inhibitors by engineered nuclease-mediated genome editing / 한국실험동물학회지
Laboratory Animal Research
;
: 264-269, 2018.
Artigo
em Inglês
| WPRIM
| ID: wpr-718841
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosfotransferases
/
Sarcoma
/
DNA
/
Ciclo Celular
/
Éxons
/
Fase G1
/
Mutagênese Insercional
/
Fases de Leitura
/
Genoma
/
Camundongos Knockout
Limite:
Animais
Idioma:
Inglês
Revista:
Laboratory Animal Research
Ano de publicação:
2018
Tipo de documento:
Artigo
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