Studies with model organisms allow experimental manipulations of genotype and environmental factors that are essential to assess causality (Aitman et al. 2011). Thus, genetic associations observed in humans or other animals can be experimentally tested using model organisms. The mouse has been the organism of choice for many such studies, but other organisms have made important contributions as well. Significant advances in the technology of mouse genetics permit several effective approaches, including generation of transgenic animals, homologous recombination to change existing genes, and more recently an international effort to generate null alleles for every gene in the mouse genome (Skarnes et al. 2011). Mouse studies are critical to understand why alleles of particular genes identified in human association studies might alter phenotypes in humans. Studies with mice also allow investigators to test environmental manipulations that would be unethical in humans, such as surgical procedures or administration of unapproved/high doses of drugs. Finally, mouse studies allow control over potential co-founding environmental factors (age, diet, drug exposure, etc.) which can reduce sources of environmental noise.
