Highly efficient CRISPR-targeting of the murine Hipp11 intergenic region supports inducible human transgene expression

Safe harbor loci allow predicable integration of a transgene into the genome without perturbing endogenous gene activity and for decades have been exploited in the mouse to investigate gene function, generate humanised models and create tissue specific reporter and Cre recombinase expressing lines. Herein, we show that the murine Hipp11 intergenic region can facilitate highly efficient integration of a large transgene-the human CD1A promoter and coding region-by means of CRISPR-Cas9 mediated homology directed repair. The data shows that the single copy human CD1A transgene is faithfully expressed in an inducible manner in homozygous animals in both macrophage and dendritic cells. Our results validate the Hipp11 intergenic region as being a highly amenable target site for functional transgene integration in mouse.