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.

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