PUBLICATION

Knockout of the hsd11b2 Gene Extends the Cortisol Stress Response in Both Zebrafish Larvae and Adults

Authors
Theodoridi, A., Dinarello, A., Badenetti, L., Pavlidis, M., Dalla Valle, L., Tsalafouta, A.
ID
ZDB-PUB-211129-59
Date
2021
Source
International Journal of Molecular Sciences   22(22): (Journal)
Registered Authors
Badenetti, Lorenzo, Dalla Valle, Luisa
Keywords
CRISPR/Cas9, LMR-L/D, VSRA, cortisol, glucocorticoid, hsd11b2, stress, zebrafish
MeSH Terms
  • Gene Knockout Techniques
  • Larva/genetics
  • Male
  • Hydrocortisone/adverse effects*
  • Hydrocortisone/pharmacology
  • Zebrafish/genetics*
  • Zebrafish/growth & development
  • Stress, Physiological/genetics*
  • Humans
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2/genetics*
  • Animals
  • Female
  • Homozygote
(all 13)
PubMed
34830405 Full text @ Int. J. Mol. Sci.
Abstract
The Hsd11b2 enzyme converts cortisol into its inactive form, cortisone and regulates cortisol levels, in particular in response to stress. Taking advantage of CRISPR/Cas9 technology, we generated a hsd11b2 zebrafish mutant line to evaluate the involvement of this gene in stress response regulation. The absence of a functional Hsd11b2 affects survival of zebrafish, although homozygous hsd11b2-/- mutants can reach adulthood. Reproductive capability of hsd11b2-/- homozygous adult males is almost completely abrogated, while that of females is reduced. Interestingly, basal cortisol levels and glucocorticoid-dependent transcriptional activities are not affected by the mutation. In agreement with basal cortisol results, we also demonstrated that basal response to light (LMR-L/D) or mechanical (VSRA) stimuli is not significantly different in wild-type (hsd11b2+/+) compared to mutant larvae. However, after exposure to an acute stressor, the cortisol temporal patterns of synthesis and release are prolonged in both 5 days post fertilization larvae and one-year-old adult hsd11b2-/- zebrafish compared to wild-type siblings, showing at the same time, at 5 dpf, a higher magnitude in the stress response at 10 min post stress. All in all, this new zebrafish model represents a good tool for studying response to different stressors and to identify mechanisms that are induced by cortisol during stress response.
Genes / Markers
Figures
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
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Mapping
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Citation
Theodoridi, A., Dinarello, A., Badenetti, L., Pavlidis, M., Dalla Valle, L., Tsalafouta, A. (2021) Knockout of the hsd11b2 Gene Extends the Cortisol Stress Response in Both Zebrafish Larvae and Adults. International Journal of Molecular Sciences. 22(22):.