Platt, R.J. et al. Cell 159, 440–455 (2014).

The clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 system—which allows easy targeting of the Cas9 nuclease via a short guide RNA—has seen many applications in modifying the genomes of differentiated cell lines and embryonic stem cells, but its application to alter the genome of somatic cells in vivo is still limited. Platt et al. now introduce an inducible expression cassette for the Cas9 nuclease into the Rosa26 locus in the mouse genome, generating a versatile tool for introducing mutations in any tissue of choice. The team achieved ex vivo genome editing in primary immune cells, in vivo targeted knockout of a neuron-specific gene and in vivo modeling of various cancer mutations, underscoring the utility of the Cas9 mouse for modeling disease.