A transgenic zebrafish model for monitoring glucocorticoid receptor activity

Gene regulation resulting from glucocorticoid receptor and glucocorticoid response element interactions is a hallmark feature of stress response signaling. Imbalanced glucocorticoid production and glucocorticoid receptor activity have been linked to socioeconomically crippling neuropsychiatric disor...

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Bibliographic Details
Published in:	Genes, brain and behavior Vol. 13; no. 5; pp. 478 - 487
Main Authors:	Krug, R. G., Poshusta, T. L., Skuster, K. J., Berg, M. R., Gardner, S. L., Clark, K. J.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-06-2014 John Wiley & Sons, Inc
Subjects:	Animals Animals, Genetically Modified - genetics Brain - metabolism Brain - physiology Circadian Rhythm cortisol Danio rerio fluticasone propionate GFP reporter line glucocorticoid receptor glucocorticoid response element HPA axis Hydrocortisone - metabolism mifepristone Mifepristone - pharmacology Osmotic Pressure Receptors, Glucocorticoid - antagonists & inhibitors Receptors, Glucocorticoid - genetics Receptors, Glucocorticoid - metabolism Response Elements stress Stress response transgenic zebrafish Zebrafish - genetics Zebrafish - metabolism Zebrafish - physiology Zebrafish Proteins - agonists Zebrafish Proteins - genetics Zebrafish Proteins - metabolism GFP reporter line cortisol stress glucocorticoid receptor transgenic zebrafish fluticasone propionate HPA axis Circadian rhythm mifepristone glucocorticoid response element
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Summary:	Gene regulation resulting from glucocorticoid receptor and glucocorticoid response element interactions is a hallmark feature of stress response signaling. Imbalanced glucocorticoid production and glucocorticoid receptor activity have been linked to socioeconomically crippling neuropsychiatric disorders, and accordingly there is a need to develop in vivo models to help understand disease progression and management. Therefore, we developed the transgenic SR4G zebrafish reporter line with six glucocorticoid response elements used to promote expression of a short half‐life green fluorescent protein following glucocorticoid receptor activation. Herein, we document the ability of this reporter line to respond to both chronic and acute exogenous glucocorticoid treatment. The green fluorescent protein expression in response to transgene activation was high in a variety of tissues including the brain, and provided single‐cell resolution in the effected regions. The specificity of these responses is demonstrated using the partial agonist mifepristone and mutation of the glucocorticoid receptor. Importantly, the reporter line also modeled the temporal dynamics of endogenous stress response signaling, including the increased production of the glucocorticoid cortisol following hyperosmotic stress and the fluctuations of basal cortisol concentrations with the circadian rhythm. Taken together, these results characterize our newly developed reporter line for elucidating environmental or genetic modifiers of stress response signaling, which may provide insights to the neuronal mechanisms underlying neuropsychiatric disorders such as major depressive disorder. Glucocorticoid signaling induces tissue‐specific, glucocorticoid receptor‐dependent transgene activation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1601-1848 1601-183X
DOI:	10.1111/gbb.12135