ZFIN ID: ZDB-PUB-150702-1
Manipulation of interrenal cell function in developing zebrafish using genetically targeted ablation and an optogenetic tool
Arturo Gutierrez-Triana, J., Herget, U., Castillo-Ramirez, L.A., Lutz, M., Yeh, C.M., De Marco, R.J., Ryu, S.
Date: 2015
Source: Endocrinology   156(9): 3394-401 (Journal)
Registered Authors: Herget, Ulrich, Ryu, Soojin
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Hydrocortisone/metabolism*
  • Interrenal Gland/metabolism*
  • Optogenetics
  • Phosphoproteins/genetics*
  • Regulatory Elements, Transcriptional*
  • Zebrafish
PubMed: 26132917 Full text @ Endocrinology
ABSTRACT
Zebrafish offer an opportunity to study conserved mechanisms underlying the ontogeny and physiology of the hypothalamic-pituitary-adrenal/interrenal (HPA/I) axis. As the final effector of the HPA/I axis, glucocorticoids (GC) exert both rapid and long-term regulatory functions. To elucidate their specific effects in zebrafish, transgenic approaches are necessary to complement pharmacological studies. Here we report a robust approach to specifically manipulate endogenous levels of cortisol by targeting heterologous proteins to interrenal cells using a promoter element of the steroidogenic acute regulatory (StAR) protein. To test this approach, we first used this regulatory region to generate a transgenic line expressing the bacterial nitroreductase protein, which allows conditional targeted ablation of interrenal cells. We demonstrate that this line can be used to ablate interrenal cells specifically, drastically reducing both basal and stress-induced cortisol levels. Next, we coupled this regulatory region with an optogenetic actuator, Beggiatoa photoactivated adenylyl cyclase to increase endogenous cortisol level in a blue-light-dependent manner. Thus, our approach allows specific manipulations of steroidogenic interrenal cell activity for studying the effects of both hypo- and hypercortisolemia in zebrafish.
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