This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schaaf, M. J. M. Articles by Richardson, M. K. Search for Related Content PubMed PubMed Citation Articles by Schaaf, M. J. M. Articles by Richardson, M. K.

Discovery of a Functional Glucocorticoid Receptor β-Isoform in Zebrafish

Departments of Molecular Cell Biology (M.J.M.S., I.H.C.v.L., D.C.W.A.v.W., A.H.M., H.P.S.) and Integrative Zoology (M.K.R.), Institute of Biology, and Division of Medical Pharmacology (D.C., O.C.M.), Leiden/Amsterdam Center for Drug Research/Leiden University Medical Center, Leiden University, 2300 RA Leiden, The Netherlands

Address all correspondence and requests for reprints to: Marcel J. M. Schaaf, Department of Molecular Cell Biology, Institute of Biology, P.O. Box 9505, 2300 RA Leiden, The Netherlands. E-mail: m.j.m.schaaf{at}biology.leidenuniv.nl.

In humans, two glucocorticoid receptor (GR) splice variants exist: GR and GRβ, which are identical between amino acids 1–727 and then diverge. Whereas GR (the canonical GR) acts as a ligand-activated transcription factor, GRβ does not bind traditional glucocorticoid agonists, lacks GR’s transactivational activity, and acts as a dominant-negative inhibitor of GR. It has been suggested that this receptor isoform is involved in the induction of glucocorticoid resistance in asthma patients. Unfortunately, a GR β-isoform has been detected in only humans, and therefore, an animal model for studies on this isoform is lacking. In the present study, we demonstrate that in zebrafish a GR isoform exists that diverges from the canonical zebrafish GR at the same position as human GRβ from human GR. The zebrafish GR β-isoform acts as a dominant-negative inhibitor in reporter assays, and the extent of inhibition and the effective GR/GRβ ratio is similar to studies performed with the human GR isoforms. In addition, the subcellular localization of zebrafish GRβ is similar to its human equivalent. Finally, expression levels of GR and GRβ were determined in adult zebrafish tissues and at several developmental stages. Both receptor isoforms were detected throughout the body, and GRβ mRNA levels were relatively low compared with GR mRNA levels, as in humans. Thus, for the first time, a GR β-isoform has been identified in a nonhuman animal species, shedding new light on the relevance of this GR splice variant and providing a versatile animal model for studies on the GR system.

This article has been cited by other articles:

				T. M. Rodela, M. D. McDonald, P. J. Walsh, and K. M. Gilmour The regulatory role of glucocorticoid and mineralocorticoid receptors in pulsatile urea excretion of the gulf toadfish, Opsanus beta J. Exp. Biol., June 15, 2009; 212(12): 1849 - 1858. [Abstract] [Full Text] [PDF]