New approaches for modelling sporadic genetic disease in the mouse.

Sporadic diseases, which occur as single, scattered cases, are among the commonest causes of human morbidity and death. They result in a variety of diseases, including many cancers, premature aging, neurodegeneration and skeletal defects. They are often pathogenetically complex, involving a mosaic distribution of affected cells, and are difficult to model in the mouse. Faithful models of sporadic diseases require innovative forms of genetic manipulation to accurately recreate their initiation and pathogenesis. Such modelling is crucial to understanding these diseases and, by extension, to the development of therapeutic approaches to treat them. This article focuses on sporadic diseases with a genetic aetiology, the challenges they pose to biomedical researchers, and the different current and developing approaches used to model such disorders in the mouse.