PUBLICATION
Manipulation of interrenal cell function in developing zebrafish using genetically targeted ablation and an optogenetic tool
- Authors
- Arturo Gutierrez-Triana, J., Herget, U., Castillo-Ramirez, L.A., Lutz, M., Yeh, C.M., De Marco, R.J., Ryu, S.
- ID
- ZDB-PUB-150702-1
- 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
Citation
Arturo Gutierrez-Triana, J., Herget, U., Castillo-Ramirez, L.A., Lutz, M., Yeh, C.M., De Marco, R.J., Ryu, S. (2015) Manipulation of interrenal cell function in developing zebrafish using genetically targeted ablation and an optogenetic tool. Endocrinology. 156(9):3394-401.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping