Aron M. GEURTS∗†‡ and Carol MORENO†‡
∗Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, U.S.A., †PhysGen Knockout Team,Human and Molecular Genetics Center, Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, U.S.A.,and ‡Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, U.S.A.

A B S T R A C T
The importance of genetic laboratory models, such as mice and rats, becomes evident when there is a poor understanding of the nature of human disease. Many rat models for human disease, created over the years by phenotype-driven strategies, now provide a foundation for the identification of their genetic determinants. These models are especially valuable with the emerging need for validation of genes found in genome-wide association studies for complex diseases. The manipulation of the rat genome using engineered zinc-finger nucleases now introduces a key technology for manipulating the rat genome, which is broadly applicable. The ability to generate knockout rat models using zinc-finger nuclease technology will now enable its full emergence as an exceptional physiological and genetic research model.