Mice in which the 5-HTT has been functionally excised either by targeted mutation or chemical mutagenesis exhibit heightened anxiety-like behavior, impaired fear extinction, and exaggerated HPA-axis responses to acute stress. While it is far less common to engineer mutant rats than mice, a 5-HTT-null mutant rat has been generated and also shows increased anxiety-like behavior (96). Furthermore, providing an interesting counterpoint to these “knockout” mutants, mice with transgenic overexpression of the 5-HTT actually produce decreased anxiety-like behavior (97). The consistency of these findings across models, laboratories, and species is rarely seen in the field of rodent behavioral genetics and illustrates the strong penetrance of the mutation’s effects.
