Mouse mutagenesis and phenotyping to generate models of development and disease

Abstract

For many years, the laboratory mouse has been the favored model organism to study mammalian development, biology and disease. Among its advantages for these studies are its close concordance with human biology, the syntenic relationship between the mouse and other mammalian genomes, the existence of many inbred strains, its short gestation period, its relatively low cost for housing and husbandry, and the wide array of tools for genome modification, mutagenesis, and for cryopreserving embryos, sperm and eggs. The advent of CRISPR genome modification techniques has considerably broadened the landscape of model organisms available for study, including other mammalian species. However, the mouse remains the most popular and utilized system to model human development, biology, and disease processes. In this review, we will briefly summarize the long history of mice as a preferred mammalian genetic and model system, and review current large-scale mutagenesis efforts using genome modification to produce improved models for mammalian development and disease.

Keywords: CRISPR/Cas9; Chemical mutagenesis; Gene knockout; High throughput; International Mouse Phenotyping Consortium; Knockout Mouse Project.