Mouse genetics/genomics: an effective approach for drug target discovery and validation

The mouse has become the premier mammalian system for the identification of the genetic basis of both mono- and oligogenic disorders, as well as the understanding of complex diseases with gene-gene and gene-environment interactions. The similarity between human and mouse genetic disease is sometimes striking, while in other cases the phenotypes are less similar. The ability to genetically map and then clone single gene disorders rapidly, and the emerging technologies that will allow the economical identification of the polygenes controlling quantitative traits further demonstrate the utility of the mouse as a model for gene discovery. Additionally, the ability to genetically manipulate the mouse through transgenesis and gene targeting allows for the testing of hypotheses regarding specific gene function and their role in disease. The utility of the mouse extends beyond being just a gene discovery tool to provide prevalidated targets. It can also be used for the development of animal models, and the testing of compounds in specifically constructed transgenic and knockout strains to further define the target and pathway of a therapeutic compound.