Knockout of the <i>hsd11b2</i> Gene Extends the Cortisol Stress Response in Both Zebrafish Larvae and Adults

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 <i>hsd11b2</i> zebrafish mutant line to evaluate the involvement of this gene in stress re...

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Autores principales:	Antonia Theodoridi, Alberto Dinarello, Lorenzo Badenetti, Michail Pavlidis, Luisa Dalla Valle, Aleka Tsalafouta
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	zebrafish stress glucocorticoid cortisol <i>hsd11b2</i> CRISPR/Cas9 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/4425acd7a5c44e578290f9888b7f8ef8
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spelling	oai:doaj.org-article:4425acd7a5c44e578290f9888b7f8ef82021-11-25T17:57:29ZKnockout of the <i>hsd11b2</i> Gene Extends the Cortisol Stress Response in Both Zebrafish Larvae and Adults10.3390/ijms2222125251422-00671661-6596https://doaj.org/article/4425acd7a5c44e578290f9888b7f8ef82021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12525https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The 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 <i>hsd11b2</i> 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 <i>hsd11b2<sup>−/−</sup></i> mutants can reach adulthood. Reproductive capability of <i>hsd11b2<sup>−/−</sup></i> 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 (<i>hsd11b2<sup>+/+</sup></i>) 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 <i>hsd11b2<sup>−/−</sup></i> 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.Antonia TheodoridiAlberto DinarelloLorenzo BadenettiMichail PavlidisLuisa Dalla ValleAleka TsalafoutaMDPI AGarticlezebrafishstressglucocorticoidcortisol<i>hsd11b2</i>CRISPR/Cas9Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12525, p 12525 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	zebrafish stress glucocorticoid cortisol <i>hsd11b2</i> CRISPR/Cas9 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	zebrafish stress glucocorticoid cortisol <i>hsd11b2</i> CRISPR/Cas9 Biology (General) QH301-705.5 Chemistry QD1-999 Antonia Theodoridi Alberto Dinarello Lorenzo Badenetti Michail Pavlidis Luisa Dalla Valle Aleka Tsalafouta Knockout of the <i>hsd11b2</i> Gene Extends the Cortisol Stress Response in Both Zebrafish Larvae and Adults
description	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 <i>hsd11b2</i> 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 <i>hsd11b2<sup>−/−</sup></i> mutants can reach adulthood. Reproductive capability of <i>hsd11b2<sup>−/−</sup></i> 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 (<i>hsd11b2<sup>+/+</sup></i>) 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 <i>hsd11b2<sup>−/−</sup></i> 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.
format	article
author	Antonia Theodoridi Alberto Dinarello Lorenzo Badenetti Michail Pavlidis Luisa Dalla Valle Aleka Tsalafouta
author_facet	Antonia Theodoridi Alberto Dinarello Lorenzo Badenetti Michail Pavlidis Luisa Dalla Valle Aleka Tsalafouta
author_sort	Antonia Theodoridi
title	Knockout of the <i>hsd11b2</i> Gene Extends the Cortisol Stress Response in Both Zebrafish Larvae and Adults
title_short	Knockout of the <i>hsd11b2</i> Gene Extends the Cortisol Stress Response in Both Zebrafish Larvae and Adults
title_full	Knockout of the <i>hsd11b2</i> Gene Extends the Cortisol Stress Response in Both Zebrafish Larvae and Adults
title_fullStr	Knockout of the <i>hsd11b2</i> Gene Extends the Cortisol Stress Response in Both Zebrafish Larvae and Adults
title_full_unstemmed	Knockout of the <i>hsd11b2</i> Gene Extends the Cortisol Stress Response in Both Zebrafish Larvae and Adults
title_sort	knockout of the <i>hsd11b2</i> gene extends the cortisol stress response in both zebrafish larvae and adults
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4425acd7a5c44e578290f9888b7f8ef8
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Knockout of the <i>hsd11b2</i> Gene Extends the Cortisol Stress Response in Both Zebrafish Larvae and Adults

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