Genetic dissection of stress response pathways in vivo.

A number of lines of evidence suggest that alterations in forebrain glucocorticoid receptor (GR)-mediated regulation of the hypothalamic-pituitary-adrenal (HPA) axis may be involved in the etiology of depression. The level of expression of GR in the hippocampus is highly correlated with HPA axis activity, and a number of animal models of depression are associated with altered forebrain GR expression. We have generated a line of mice with a conditional, forebrain-specific deletion of GR (FBGRKO) to determine if a primary deficit in forebrain GR signaling is an etiologic factor in the pathogenesis of depression. These mice should prove to be valuable for identifying GR target genes in major depressive disorder (MDD) and testing pharmacological agents for efficacy in this disorder.