CRISPR-Cas9 knockin mice for genome editing and cancer modeling.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 25263330.
- Also identified by DOI 10.1016/j.cell.2014.09.014 and PMC identifier 4265475.
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Abstract
CRISPR-Cas9 is a versatile genome editing technology for studying the functions of genetic elements. To broadly enable the application of Cas9 in vivo, we established a Cre-dependent Cas9 knockin mouse. We demonstrated in vivo as well as ex vivo genome editing using adeno-associated virus (AAV)-, lentivirus-, or particle-mediated delivery of guide RNA in neurons, immune cells, and endothelial cells. Using these mice, we simultaneously modeled the dynamics of KRAS, p53, and LKB1, the top three significantly mutated genes in lung adenocarcinoma. Delivery of a single AAV vector in the lung generated loss-of-function mutations in p53 and Lkb1, as well as homology-directed repair-mediated Kras(G12D) mutations, leading to macroscopic tumors of adenocarcinoma pathology. Together, these results suggest that Cas9 mice empower a wide range of biological and disease modeling applications.
Medical subject headings
- Adenocarcinoma
- Disease Models, Animal
- Genes, Tumor Suppressor
- Genetic Engineering
- Lung Neoplasms
- Oncogenes