ABSENCE OF GLUCOCORTICOID RECEPTOR-BETA IN MICE

Two human glucocorticoid receptor (GR) isoforms, GR alpha and GR beta, are derived from the same gene by alternative splicing involving exon 9 of the GR locus, The non-ligand binding isoform GR beta was propose d to act as a transdominant negative inhibitor of GR alpha, thus modul ating glucocorticoid responsiveness of target tissues, To study GR bet a in mice we characterized the genomic region around exon 9 of the mur ine GR gene. Sequence analysis revealed that the presumed exon 9 beta contained an open reading frame of 59 amino acids, In contrast, human exon 9 beta encoded only 15 amino acids, Using reverse transcriptase p olymerase chain reaction the ab absence of GR beta mRNA was demonstrat ed in all adult mouse tissues examined, To exclude the possibility tha t the polymerase chain reaction conditions employed were not suitable for the amplification of GR beta mRNA, we synthesized an artificial te mplate corresponding to the presumed GRP mRNA spanning exons 7, 8, and 9 beta, Various amounts of this template were added to brain cDNA pre parations and as little as 25 molecules were detectable under the poly merase chain reaction conditions chosen, Since GR beta is not conserve d across species its physiological significance in humans appears ques tionable.