Over the past 20 years, the UK has become a leading force in the generation and use of complex mouse models in the precise investigation of human disease. Nevertheless, there remains a great challenge in improving how research in animals is translated to clinical benefits. Developing and expanding connections between basic scientists and clinicians to ensure that animal models accurately recapitulate human disease will be key to this effort. This is the focus of the new UK Medical Research Council (MRC) National Mouse Genetics Network (https://nmgn.mrc.ukri.org/), which we believe will hugely impact our ability to harness recent advances in mouse genetics. The National Mouse Genetics Network is a major £22 million investment initially comprising seven challenge-led research clusters with members distributed across the UK. At its core, the Mary Lyon Centre at MRC Harwell will act as a repository for, and provider of, genetically altered mice, as well as generate and share data, training, specialist facilities and resources. Importantly, each cluster will integrate expertise in fundamental biology with clinical findings to better address pertinent research questions. Results from previous, smaller-scale, network initiatives suggest that this model can synergise research, but we believe that this structure will work better when carried out on a larger scale, with greater scope for collaboration and capacity of the system. This Editorial will outline the principal aims of the Network and identify the main areas in which this model will be able to exploit the power and synergy of its different elements.