Glucocorticoid transcriptome in the hippocampus of wild-type and GRA knockin mice

In addition to the classic full-length GR isoform (GRA), seven highly conserved receptor isoforms (GRB, GRC1, GRC2, GRC3, GRD1, GRD2, and GRD3) with progressively shorter amino-terminal transactivation domains (NTD) are produced from the single GR gene by alternative translation initiation. The in vivo function of these seven GR NTD translational isoforms remains unknown.

To elucidate the physiological function of the GR NTD translational isoforms, we developed mice (GRA knockin) that express the GRA isoform but not the GRB, GRC1, GRC2, GRC3, GRD1, GRD2, and GRD3 translational isoforms. RNA-seq was performed on RNA isolated from the whole hippocampus of wild-type (WT) and GRA knockin mice treated with vehicle or the synthetic glucocorticoid dexamethasone (Dex) in an effort to determine how the GR NTD translational isoforms impact the glucocorticoid transcriptome.