Altered Affective Behaviors in Casein Kinase 1 Epsilon Mutant Mice

Affective behaviors and mental health are profoundly affected by disturbances in circadian rhythms. Casein kinase 1 epsilon (CSNK1E) is an essential component of the core circadian clock. Mice with point mutation or null mutation of this gene have shortened and lengthened circadian period respectively. Here we examined anxiety-like, fear, and depressive-like behaviors in both male and female mice of these two different mutants. Compared with wild-type mice, we found reductions in fear and anxiety-like behaviors in both mutant lines and in both sexes, with the mutants exhibiting the greatest phenotypic changes. Female null mutants showed markedly less depressive-like behaviors than wild-type mice, but these differences were not observed in mutants of either sex. To determine whether abnormal light entrainment of mutants to 24 hour light-dark cycles contributes to these phenotypic differences, we also examined these behaviors in mutants on a light-dark cycle that close to their endogenous circadian period. The normalized entrainment restored more wild type-like behaviors for fear and anxiety, but it induced depressive-like behavior in females. These data show that both mutations of broadly affect fear and anxiety-like behaviors, while the effects on depressive-like behavior vary with genetics, entrainment, and sex. This suggests that the mechanisms by which affects fear and anxiety-like behaviors may be similar, but distinct from those affecting depressive-like behavior. Taken together, these findings demonstrate that a dysfunctional circadian pacemaker can significantly alter affective behaviors, and thus, be a risk factor for affective disorders.