Functional analysis reveals no transcriptional role for the glucocorticoid receptor β-isoform in zebrafish

- The zebrafish GRβ is a dominant-negative inhibitor of GRα in reporter assays.
- No inhibition of GRα is observed in assays measuring endogenous gene expression.
- A transgenic zebrafish line was generated with inducible GRβ expression.
- Using this line, no effect of GRβ on the transcriptome was observed.

In humans, two splice variants of the glucocorticoid receptor (GR) exist: the canonical α-isoform, and the β-isoform, which has been shown to have a dominant-negative effect on hGRα. Previously, we have established the occurrence of a GR β-isoform in zebrafish, and in the present study we have investigated the functional role of the zebrafish GRβ (zGRβ). Reporter assays in COS-1 cells demonstrated a dominant-negative effect of zGRβ but no such effect was observed in zebrafish PAC2 cells using induction of the fk506 binding protein 5 (fkbp5) gene as readout. Subsequently, we generated a transgenic fish line with inducible expression of zGRβ. Transcriptome analysis suggested transcriptional regulation of genes by zGRβ in this line, but further validation failed to confirm this role. Based on these results, its low expression level and its poor evolutionary conservation, we suggest that the zebrafish GR β-isoform does not have a functional role in transcriptional regulation.