| First Author | Jager J | Year | 2014 |
| Journal | Mol Endocrinol | Volume | 28 |
| Issue | 4 | Pages | 490-8 |
| PubMed ID | 24552589 | Mgi Jnum | J:213068 |
| Mgi Id | MGI:5582847 | Doi | 10.1210/me.2013-1351 |
| Citation | Jager J, et al. (2014) Behavioral changes and dopaminergic dysregulation in mice lacking the nuclear receptor Rev-erbalpha. Mol Endocrinol 28(4):490-8 |
| abstractText | The regulation of behavior by the molecular components of the circadian clock is not well understood. Here we report that mice lacking the nuclear receptor Rev-erbalpha, a potent transcriptional repressor and core clock component, displayed marked hyperactivity and impaired response habituation in novel environments. In addition, Rev-erbalpha knockout (KO) mice were deficient in short-term, long-term, and contextual memories and also showed impairment in nest-building ability. Together, these results suggest that Rev-erbalpha KO mice manifest defective hippocampal function. Interestingly, the changes in novelty-induced locomotor activity of Rev-erbalpha KO mice were comparable at multiple times of day, potentially due to the muted amplitude of Rev-erbalpha oscillation in the hippocampus of wild-type mice. Hippocampal dopamine turnover was increased in Rev-erbalpha KO mice, due to up-regulation of tyrosine hydroxylase, the rate-limiting enzyme in dopamine production, and pharmacologic inhibition of tyrosine hydroxylase activity partially rescued locomotor hyperactivity. These findings reveal a novel, nonredundant function for Rev-erbalpha that links a core component of the circadian gene-regulatory network to the control of dopaminergic and hippocampus-dependent behaviors. |
