A transgenic zebrafish model for monitoring glucocorticoid receptor activity

II G. Krug, T. L. Poshusta, K. J. Skuster, M. R. Berg, S. L. Gardner, K. J. Clark

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)478-487
Number of pages10
JournalGenes, Brain and Behavior
Volume13
Issue number5
DOIs
StatePublished - 2014

Keywords

  • Circadian rhythm
  • Cortisol
  • Fluticasone propionate
  • GFP reporter line
  • Glucocorticoid receptor
  • Glucocorticoid response element
  • HPA axis
  • Mifepristone
  • Stress
  • Transgenic zebrafish

ASJC Scopus subject areas

  • Genetics
  • Neurology
  • Behavioral Neuroscience

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  • Cite this

    Krug, II. G., Poshusta, T. L., Skuster, K. J., Berg, M. R., Gardner, S. L., & Clark, K. J. (2014). A transgenic zebrafish model for monitoring glucocorticoid receptor activity. Genes, Brain and Behavior, 13(5), 478-487. https://doi.org/10.1111/gbb.12135