Gene Changes in Hippocampus from Mice with Conditional Knockout of Hippocampal GR, MR, or both GR and MR

Glucocorticoids are primary stress hormones that have been implicated in the pathogenesis of cognitive impairments and psychiatric illnesses. The hippocampus expresses high levels of glucocorticoid (GR) and mineralocorticoid receptors (MR) which both bind glucocorticoids. However, the specific and cooperative roles played by GR and MR in mediating the direct actions of stress on the hippocampus are unknown. To elucidate the function of hippocampal GR and MR, we generated mice with conditional knockout of GR (GREmx1-cre), MR (MREmx1-cre), or both GR and MR (GRMREmx1-cre) in the hippocampus. Genome-wide microarrays were performed on RNA isolated from the whole hippocampus to 1) identify genes subject to regulation by GR alone, MR alone, or both GR and MR and 2) identify the genes responsible for the morphological and behavioral phenotypes observed in these mice. Mice harboring a floxed GR allele (GRflox), MR allele (MRflox), or both GR and MR alleles (dflox) were crossed with Emx1-Cre mice to generate mice lacking GR (GREmx1-cre), MR (MREmx1-cre), or both GR and MR (GRMREmx1-cre) in the hippocampus, respectively. Total RNA for microarray analysis was harvested from the whole hippocampus isolated from approximately 2.5-month old male dflox control mice and GREmx1-cre, MREmx1-cre, and GRMREmx1-cre knockout mice.