Absence of glucocorticoid receptor-β in mice

Abstract

Two human glucocorticoid receptor (GR) isoforms, GRα and GRβ, are derived from the same gene by alternative splicing involving exon 9 of the GR locus. The non-ligand binding isoform GRβ was proposed to act as a transdominant negative inhibitor of GRα, thus modulating glucocorticoid responsiveness of target tissues. To study GRβ in mice we characterized the genomic region around exon 9 of the murine GR gene. Sequence analysis revealed that the presumed exon 9β contained an open reading frame of 59 amino acids. In contrast, human exon 9β encoded only 15 amino acids. Using reverse transcriptase polymerase chain reaction the absence of GRβ mRNA was demonstrated in all adult mouse tissues examined. To exclude the possibility that the polymerase chain reaction conditions employed were not suitable for the amplification of GRβ mRNA, we synthesized an artificial template corresponding to the presumed GRβ mRNA spanning exons 7, 8, and 9β. Various amounts of this template were added to brain cDNA preparations and as little as 25 molecules were detectable under the polymerase chain reaction conditions chosen. Since GRβ is not conserved across species its physiological significance in humans appears questionable.