Many stress-related neuropsychiatric disorders display pronounced sex differences in their frequency and clinical symptoms. Glucocorticoids are primary stress hormones that have been implicated in the development of these disorders but whether they contribute to the observed sex bias is poorly understood. Glucocorticoids signal through two closely related nuclear receptors, the glucocorticoid (GR) and mineralocorticoid receptor (MR), that are both expressed at high levels in the hippocampus. To investigate the sex-dependent and independent actions of glucocorticoids in the hippocampus, we developed knockout mice lacking hippocampal GR (GREmx1-cre), MR (MREmx1-cre), or both GR and MR (GRMREmx1-cre). Genome-wide microarrays were performed on RNA isolated from the hippocampus of male and female flox control and knockout mice in order to 1) identify genes dysregulated in a sex-dependent and independent manner by a deficiency in GR, MR, or both GR and MR signaling and 2) identify the genes responsible for the sex-dependent and independent phenotypes observed in these mice.
Overall design
Mice harboring a floxed GR allele and MR allele (dflox) and mice with conditional knockout of the glucocorticoid receptor (GR) (GREmx1-cre), mineralocorticoid receptor (MR) (MREmx1-cre), or both GR and MR (GRMREmx1-cre) in the hippocampus have been previously described (Oakley et al, Neurobiol Stress.2021 Jul 21;15:100369.doi: 10.1016/j.ynstr.2021.100369). For this microarray, total RNA was isolated from the whole hippocampus of adult male and female dflox control, GREmx1-cre, MREmx1-cre, and GRMREmx1-cre mice (n = 3-4 mice per genotype).
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