The zebrafish as a model system for glucocorticoid receptor research

Glucocorticoids regulate a plethora of physiological processes, and are widely used clinically as anti-inflammatory drugs. Their effects are mediated by the glucocorticoid receptor (GR), a ligand-activated transcription factor. Currently, zebrafish embryos are being developed into a model system for GR research, since they are easy to manipulate genetically and their phenotype can easily be visualized because of their transparent bodies. In addition, the zebrafish GR gene shows a relatively high level of similarity with its human equivalent. First, both the zebrafish and the human genome contain only a single gene encoding the GR. In all other fish species studied thus far, two GR genes have been found. Second, the zebrafish contains a C-terminal GR splice variant with high similarity to the human GRbeta, which has been shown to be a dominant-negative inhibitor of the canonical GRalpha and may be involved in glucocorticoid resistance. Thus, zebrafish embryos are potentially a useful model system for glucocorticoid receptor research, but currently only a limited number of tools is available. In this review, we discuss which tools are available and which need to be developed, in order to exploit the full potential of the zebrafish as a model system for GR research.