that Rev-erbα deficient mice no longer exhibit these oscillations, notably in IL-6, IL-12, CCL5, and CXCL1, and CCL2. Rev-erbα has also been implicated in the development of group 3 innate lymphoid cells (ILC3), which play a role in regulating intestinal health and are responsible for lymphoid development. REV-ERBα promotes RORγt expression, and RORγt is required for ILC3 expression. Rev-erbα is highly expressed in ILC3 subsets. Mood and behavior Rev-erbα has been implicated in the regulation of memory and mood. Rev-erbα knockout mice are deficient in short term, long term, and contextual memories, showing deficits in the function of their hippocampus. In addition, Rev-erbα has been proposed to play a role in the regulation of midbrain dopamine production and mood-related behavior in mice through repression of tyrosine hydroxylase gene transcription. Dopamine related dysfunction is associated with mood disorders, notably major depressive disorder, seasonal affective disorder, and bipolar disorder. Genetic variations in human NR1D1 loci are also associated with bipolar disorder onset. Rev-erbα has been proposed as a target in the treatment of bipolar disorder through lithium, which indirectly regulates the protein at a post-translational level. Lithium inhibits glycogen synthase kinase (GSK 3β), an enzyme that phosphorylates and stabilizes Rev-erbα. Lithium binding to GSK 3β then destabilizes and alters the function of Rev-erbα. This research has been implicated in the development of therapeutic agents for affective disorders, such as lithium for bipolar disorder. References Further reading External links Intracellular receptors Transcription factors