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 u nderstanding of complex diseases with gene-gene and gene-environment intera ctions. The similarity between human and mouse genetic disease is sometimes striking, while in ether cases the phenotypes are less similar. The abilit y 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 o f the mouse as a model for gene discovery, Additionally, the ability to gen etically manipulate the mouse through transgenesis and gene targeting allow s 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 a nd pathway of a therapeutic compound. (C) 2000 John Wiley & Sons, inc.