Modeling Genetic Susceptibility to Disease

As we transition to an era of personalized medicine, it has become imperative to integrate genomics with pharmacological and toxicological discoveries to provide individualized care to patients. Animal models are extremely important in understanding this interface as well as in bridging the gap between basic science discoveries and clinical medicine. The complex nature of pharmacological and toxicological research involving exposure to xenobiotic and therapeutic compounds necessitates the use of animal models to better understand how these compounds interact with multiple organ systems and cell types. As genomics has expanded, we have become increasingly aware of the impact an individual’s genetic makeup influences these responses. Novel methods have emerged that allow for the rapid development of animal models containing mutant alleles, allowing investigators to model these complex genetic interactions in a dramatically shortened timeline. In this chapter, we emphasize the methods and approaches that can be used in gene targeting, screening strategies, and a variety of genetically modified model organisms. The goal is to provide toxicologists an up to date review on the creation of genetically engineered animal models, which can be used to model genetic susceptibility to disease.