An approach to mental disorders using model mice

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Previously, we identified ubiquitin specific peptidase 46 (Usp46) as one of the genes responsible for reductions in time spent immobile behavior in the tail suspension and forced swim test. This gene is involved in the regulation of not only immobility but also many other behavioral phenotypes. In this study, in order to understand physiological and biochemical mechanisms of behavioral disorders caused by Usp46 mutation, we studied Usp46 mutant mice from both genetic and environmental points of view. As a result, we found that Usp46 is expressed in a number of brain regions and regulates several behavioral phenotypes through GABAergic system. We also found that Usp46 mice are vulnerable to stress, and exhibit poor maternal behavior. Poor maternal behavior, however, can improve if adequate postpartum maternal care is given, even in these genetically vulnerable mice.