PUBLICATION

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

Authors
Facchinello, N., Skobo, T., Meneghetti, G., Colletti, E., Dinarello, A., Tiso, N., Costa, R., Gioacchini, G., Carnevali, O., Argenton, F., Colombo, L., Dalla Valle, L.
ID
ZDB-PUB-170701-5
Date
2017
Source
Scientific Reports   7: 4371 (Journal)
Registered Authors
Argenton, Francesco, Carnevali, Oliana, Colletti, Elisa, Costa, Roberto, Dalla Valle, Luisa, Facchinello, Nicola, Skobo, Tatjana, Tiso, Natascia
Keywords
Adrenal cortex hormones, Disease model, Endocrine system and metabolic diseases
MeSH Terms
none
PubMed
28663543 Full text @ Sci. Rep.
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.
Genes / Markers
Figures
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes