Mouse models of human disease. Part I: techniques and resources for genetic analysis in mice.

Abstract

The mouse is an ideal model organism for human disease. Not only are mice physiologically similar to humans, but a large genetic reservoir of potential models of human disease has been generated through the identification of >1000 spontaneous, radiation- or chemically induced mutant loci. In addition, a number of recent technological advances have dramatically increased our ability to create mouse models of human disease. These technological advances include the development of highresolution genetic and physical linkage maps of the mouse genome, which in turn are facilitating the identification and cloning of mouse disease loci. Furthermore, transgenic technologies that allow one to ectopically express or make germ-line mutations in virtually any gene in the mouse genome have been developed, as well as methods for analyzing complex genetic diseases. In Part I of this review, we summarize some of the classical and modern approaches that have fueled the recent dramatic explosion in mouse disease model development. In Part II of this review, we list >100 mouse models of human disease where the homologous gene has been shown to be mutated in both human and mouse (Bedell et al., this issue). In the vast majority of these models, the mouse mutant phenotype very closely resembles the human disease phenotype and these models therefore provide valuable resources to understand how the diseases develop and to test ways to prevent or treat these diseases. Additionally, we highlight a number of areas of this research where significant progress has been made in the past few years.