Other evidence relevant to ANK3’s possible involvement in psychiatric traits comes from a recent mouse model study by Leussis et al. 2012 that examined the behavioral effects of perturbed expression of the mouse ortholog of the ANK3 gene (Ank3) (Leussis et al., 2012a). Mice with 40% lower expression of ankyrin G brain-specific isoforms exhibited significantly altered behaviors in explicit domains. Specifically, compared to wild-type Ank3+/+ mice with normal ankyrin G expression, Ank3+/− mice with reduced expression rapidly entered aversive environments in several tasks that present a conflict between exploration motivated by natural rewards (e.g., finding food, mates) and avoidance behavior in the presence of threat cues, and they also displayed increased consumption of a food reward in a safe environment. One possible interpretation of these findings is an increase in behavioral disinhibition associated with Ank3 suppression in brain. Interestingly, when exposed to chronic stress, the behavioral changes of Ank3+/− mice were reversed and depression-related features emerged (increased immobility in the forced swim test). In contrast, wild-type Ank3+/+ mice were unaffected by the stress exposure, suggesting that reduced expression of ankyrin
