nr3c1 null mutant zebrafish are viable and reveal DNA-binding-independent activities of the glucocorticoid receptor

Abstract Glucocorticoids (GCs) play important roles in developmental and physiological processes through the transcriptional activity of their cognate receptor (Gr). Using CRISPR/Cas9 technology, we established a zebrafish null Gr mutant line and compared its phenotypes with wild type and a zebrafis...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	N. Facchinello, T. Skobo, G. Meneghetti, E. Colletti, A. Dinarello, N. Tiso, R. Costa, G. Gioacchini, O. Carnevali, F. Argenton, L. Colombo, L. Dalla Valle
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5fc0ac8c9079415a80ca8b2300792049
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5fc0ac8c9079415a80ca8b2300792049
record_format	dspace
spelling	oai:doaj.org-article:5fc0ac8c9079415a80ca8b23007920492021-12-02T15:06:03Znr3c1 null mutant zebrafish are viable and reveal DNA-binding-independent activities of the glucocorticoid receptor10.1038/s41598-017-04535-62045-2322https://doaj.org/article/5fc0ac8c9079415a80ca8b23007920492017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04535-6https://doaj.org/toc/2045-2322Abstract Glucocorticoids (GCs) play important roles in developmental and physiological processes through the transcriptional activity of their cognate receptor (Gr). Using CRISPR/Cas9 technology, we established a zebrafish null Gr mutant line and compared its phenotypes with wild type and a zebrafish line with partially silenced gr (gr s357/s357 ). Homozygous gr −/− larvae are morphologically inconspicuous and, in contrast to GR −/− knockout mice, viable through adulthood, although with reduced fitness and early life survival. Mutants gr −/− are fertile, but their reproductive capabilities fall at around 10 months of age, when, together with cardiac and intestinal abnormalities already visible at earlier stages, increased fat deposits are also observed. Mutants show higher levels of whole-body cortisol associated with overstimulated basal levels of crh and pomca transcripts along the HPI axis, which is unresponsive to a mechanical stressor. Transcriptional activity linked to immune response is also hampered in the gr −/− line: after intestinal damage by dextran sodium sulphate exposure, there are neither inflammatory nor anti-inflammatory cytokine gene responses, substantiating the hypothesis of a dual-action of the GC-GR complex on the immune system. Hence, the zebrafish gr mutant line appears as a useful tool to investigate Gr functions in an integrated in vivo model.N. FacchinelloT. SkoboG. MeneghettiE. CollettiA. DinarelloN. TisoR. CostaG. GioacchiniO. CarnevaliF. ArgentonL. ColomboL. Dalla ValleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q N. Facchinello T. Skobo G. Meneghetti E. Colletti A. Dinarello N. Tiso R. Costa G. Gioacchini O. Carnevali F. Argenton L. Colombo L. Dalla Valle nr3c1 null mutant zebrafish are viable and reveal DNA-binding-independent activities of the glucocorticoid receptor
description	Abstract Glucocorticoids (GCs) play important roles in developmental and physiological processes through the transcriptional activity of their cognate receptor (Gr). Using CRISPR/Cas9 technology, we established a zebrafish null Gr mutant line and compared its phenotypes with wild type and a zebrafish line with partially silenced gr (gr s357/s357 ). Homozygous gr −/− larvae are morphologically inconspicuous and, in contrast to GR −/− knockout mice, viable through adulthood, although with reduced fitness and early life survival. Mutants gr −/− are fertile, but their reproductive capabilities fall at around 10 months of age, when, together with cardiac and intestinal abnormalities already visible at earlier stages, increased fat deposits are also observed. Mutants show higher levels of whole-body cortisol associated with overstimulated basal levels of crh and pomca transcripts along the HPI axis, which is unresponsive to a mechanical stressor. Transcriptional activity linked to immune response is also hampered in the gr −/− line: after intestinal damage by dextran sodium sulphate exposure, there are neither inflammatory nor anti-inflammatory cytokine gene responses, substantiating the hypothesis of a dual-action of the GC-GR complex on the immune system. Hence, the zebrafish gr mutant line appears as a useful tool to investigate Gr functions in an integrated in vivo model.
format	article
author	N. Facchinello T. Skobo G. Meneghetti E. Colletti A. Dinarello N. Tiso R. Costa G. Gioacchini O. Carnevali F. Argenton L. Colombo L. Dalla Valle
author_facet	N. Facchinello T. Skobo G. Meneghetti E. Colletti A. Dinarello N. Tiso R. Costa G. Gioacchini O. Carnevali F. Argenton L. Colombo L. Dalla Valle
author_sort	N. Facchinello
title	nr3c1 null mutant zebrafish are viable and reveal DNA-binding-independent activities of the glucocorticoid receptor
title_short	nr3c1 null mutant zebrafish are viable and reveal DNA-binding-independent activities of the glucocorticoid receptor
title_full	nr3c1 null mutant zebrafish are viable and reveal DNA-binding-independent activities of the glucocorticoid receptor
title_fullStr	nr3c1 null mutant zebrafish are viable and reveal DNA-binding-independent activities of the glucocorticoid receptor
title_full_unstemmed	nr3c1 null mutant zebrafish are viable and reveal DNA-binding-independent activities of the glucocorticoid receptor
title_sort	nr3c1 null mutant zebrafish are viable and reveal dna-binding-independent activities of the glucocorticoid receptor
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5fc0ac8c9079415a80ca8b2300792049
work_keys_str_mv	AT nfacchinello nr3c1nullmutantzebrafishareviableandrevealdnabindingindependentactivitiesoftheglucocorticoidreceptor AT tskobo nr3c1nullmutantzebrafishareviableandrevealdnabindingindependentactivitiesoftheglucocorticoidreceptor AT gmeneghetti nr3c1nullmutantzebrafishareviableandrevealdnabindingindependentactivitiesoftheglucocorticoidreceptor AT ecolletti nr3c1nullmutantzebrafishareviableandrevealdnabindingindependentactivitiesoftheglucocorticoidreceptor AT adinarello nr3c1nullmutantzebrafishareviableandrevealdnabindingindependentactivitiesoftheglucocorticoidreceptor AT ntiso nr3c1nullmutantzebrafishareviableandrevealdnabindingindependentactivitiesoftheglucocorticoidreceptor AT rcosta nr3c1nullmutantzebrafishareviableandrevealdnabindingindependentactivitiesoftheglucocorticoidreceptor AT ggioacchini nr3c1nullmutantzebrafishareviableandrevealdnabindingindependentactivitiesoftheglucocorticoidreceptor AT ocarnevali nr3c1nullmutantzebrafishareviableandrevealdnabindingindependentactivitiesoftheglucocorticoidreceptor AT fargenton nr3c1nullmutantzebrafishareviableandrevealdnabindingindependentactivitiesoftheglucocorticoidreceptor AT lcolombo nr3c1nullmutantzebrafishareviableandrevealdnabindingindependentactivitiesoftheglucocorticoidreceptor AT ldallavalle nr3c1nullmutantzebrafishareviableandrevealdnabindingindependentactivitiesoftheglucocorticoidreceptor
_version_	1718388585466429440

nr3c1 null mutant zebrafish are viable and reveal DNA-binding-independent activities of the glucocorticoid receptor

Ejemplares similares