Research using rodents allows for experimental control over genetic background and the environment to a degree that is neither practically nor ethically feasible in human or even nonhuman primate studies (93). Although there is functional gene variation in the murine 5-HTT (slc6a4) (94), there is no rodent orthologue of the 5-HTTLPR. As an alternative approach, mice and rats have been genetically engineered with loss-of-function mutations in the 5-HTT gene. Studying the consequences of these mutations for behavior and brain function has greatly complemented the work on the 5-HTTLPR in primates and provided some key insights into the mechanisms that mediate the influence of 5-HTT on negative affect and stress reactivity (56, 95).
