Humanising the mouse genome piece by piece

To better understand human health and disease, researchers create a wide variety of mouse models that carry human DNA. With recent advances in genome engineering, the targeted replacement of mouse genomic regions with orthologous human sequences has become increasingly viable, ranging from finely tuned humanisation of individual nucleotides and amino acids to the incorporation of many megabases of human DNA. Here, we examine emerging technologies for targeted genomic humanisation, we review the spectrum of existing genomically humanised mouse models and the insights such models have provided, and consider the lessons learned for designing such models in the future.
Generation of transgenic mice has become routine in studying gene function and disease mechanisms, but often this is not enough to fully understand human biology. Here, the authors review the current state of the art of targeted genomic humanisation strategies and their advantages over classic approaches.