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.
Highlights
Both in humans and teleosts, is the primary glucocorticoid involved in stress response
The hsd11b2 mutant zebrafish line generated with CRISPR/Cas9 technology is characterized by an insertion of 19 nucleotides in the first coding exon of the hsd11b2 gene (Figure 1)
It is well established that the coordinated HPI axis regulation of cortisol stress response
Summary
As in the case of other animals, the HPI activation leads to the release of catecholamines and cortisol as the primary response, adjustments in physiology and metabolism as the secondary response and, changes at the whole animal or population level as part of the tertiary response [3,4]. Cortisol, both in humans and teleosts, is the primary glucocorticoid involved in stress response. Adult zebrafish show a dynamic response to stress with a very rapid and prolonged increase in whole-body cortisol concentrations, starting at around 15 min and returning to basal levels at about 2 h following exposure to acute stressors [6]
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