Genetic rat models for schizophrenia

In the present chapter, we have discussed the current state of genetic modeling in rats in general and for schizophrenia in particular. The establishment of gene targeting technology in rat ES cells, in combination with advances in genomics and the vast amount of research data on physiology and pharmacology in this species, now provides a powerful new platform for the study of human disease. The rat offers a complementary model choice to the mouse because rat models have been shown to more closely mimic human disease than mouse models in several areas such as neurodegenerative diseases, hypertension, and Huntington’s disease (reviewed in Lu et al., 2007). For example, there are clear differences between the SERT knockout rat and the SERT knockout mouse (see the previous section). Likewise, we have recently found clear differences between the BACHD rat and mouse models for Huntington’s disease (Abada, Nguyen, Schreiber, & Ellenbroek, 2013; Abada, Schreiber, & Ellenbroek, 2013). The rat is the model of choice in diverse areas of biomedical research such as cardiovascular diseases, pharmacology, behavioral/addiction studies, and neurobiology (Gibbs et al., 2004; Tesson et al., 2005). Moreover, rats are approximately 10 times larger than mice, allowing investigators to perform procedures such as nerve recordings, collection of tissue from small structures, and serial blood sampling more easily. Finally, their cognitive and social performance is much closer related to the human condition than mice (Abbott, 2004). In relation to complex disorder such as schizophrenia, we do, however, need to realize the limitations of genetic modeling.