RGD Reference Report - Conditional deletion of glucocorticoid receptors in rat brain results in sex-specific deficits in fear and coping behaviors. - Rat Genome Database

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Conditional deletion of glucocorticoid receptors in rat brain results in sex-specific deficits in fear and coping behaviors.

Authors: Scheimann, Jessie R  Moloney, Rachel D  Mahbod, Parinaz  Morano, Rachel L  Fitzgerald, Maureen  Hoskins, Olivia  Packard, Benjamin A  Cotella, Evelin M  Hu, Yueh-Chiang  Herman, James P 
Citation: Scheimann JR, etal., Elife. 2019 Jul 22;8:e44672. doi: 10.7554/eLife.44672.
RGD ID: 407571699
Pubmed: PMID:31329100   (View Abstract at PubMed)
PMCID: PMC6645713   (View Article at PubMed Central)
DOI: DOI:10.7554/eLife.44672   (Journal Full-text)

Glucocorticoid receptors (GR) have diverse functions relevant to maintenance of homeostasis and adaptation to environmental challenges. Understanding the importance of tissue-specific GR function in physiology and behavior has been hampered by near-ubiquitous localization in brain and body. Here we use CRISPR/Cas9 gene editing to create a conditional GR knockdown in Sprague Dawley rats. To test the impact of cell- and region-specific GR knockdown on physiology and behavior, we targeted GR knockdown to output neurons of the prelimbic cortex. Prelimbic knockdown of GR in females caused deficits in acquisition and extinction of fear memory during auditory fear conditioning, whereas males exhibited enhanced active-coping behavior during forced swim. Our data support the utility of this conditional knockdown rat to afford high-precision knockdown of GR across a variety of contexts, ranging from neuronal depletion to circuit-wide manipulations, leveraging the behavioral tractability and enhanced brain size of the rat as a model organism.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NR3C1Humandepressive disorder sexual_dimorphismISONr3c1 (Rattus norvegicus) RGD 
Nr3c1Ratdepressive disorder sexual_dimorphismIMP  RGD 
Nr3c1Mousedepressive disorder sexual_dimorphismISONr3c1 (Rattus norvegicus) RGD 
Nr3c1em1KuanRatdepressive disorder sexual_dimorphismIMP  RGD 
SD-Nr3c1em1KuanRatdepressive disorder sexual_dimorphismIMP  RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nr3c1Ratassociative learning  IMP  RGD 
Nr3c1Ratnegative regulation of behavioral fear response  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nr3c1Ratenhanced cued conditioning behavior sexual_dimorphismIMP associated with abnormal freezing behavior MP:0020420 and compared to female wild type littermateRGD 
Nr3c1em1KuanRatenhanced cued conditioning behavior sexual_dimorphismIMP associated with abnormal freezing behavior MP:0020420 and compared to female wild type littermateRGD 
SD-Nr3c1em1KuanRatenhanced cued conditioning behavior sexual_dimorphismIMP associated with abnormal freezing behavior MP:0020420 and compared to female wild type littermateRGD 
Nr3c1Ratincreased circulating corticosterone level sexual_dimorphismIMPphysical restraint in tube type rodent restrainercompared to female wild type littermateRGD 
Nr3c1em1KuanRatincreased circulating corticosterone level sexual_dimorphismIMPphysical restraint in tube type rodent restrainercompared to female wild type littermateRGD 
SD-Nr3c1em1KuanRatincreased circulating corticosterone level sexual_dimorphismIMPphysical restraint in tube type rodent restrainercompared to female wild type littermateRGD 
Nr3c1Ratincreased coping response sexual_dimorphismIMPforced swimmingcompared to male wild type littermateRGD 
Nr3c1em1KuanRatincreased coping response sexual_dimorphismIMPforced swimmingcompared to male wild type littermateRGD 
SD-Nr3c1em1KuanRatincreased coping response sexual_dimorphismIMPforced swimmingcompared to male wild type littermateRGD 
Nr3c1Ratincreased freezing behavior sexual_dimorphismIMP compared to female wild type littermateRGD 
Nr3c1em1KuanRatincreased freezing behavior sexual_dimorphismIMP compared to female wild type littermateRGD 
SD-Nr3c1em1KuanRatincreased freezing behavior sexual_dimorphismIMP compared to female wild type littermateRGD 
Nr3c1Ratslow extinction of fear memory sexual_dimorphismIMP associated with abnormal freezing behavior MP:0020420 and compared to female wild type littermateRGD 
Nr3c1em1KuanRatslow extinction of fear memory sexual_dimorphismIMP associated with abnormal freezing behavior MP:0020420 and compared to female wild type littermateRGD 
SD-Nr3c1em1KuanRatslow extinction of fear memory sexual_dimorphismIMP associated with abnormal freezing behavior MP:0020420 and compared to female wild type littermateRGD 
Objects Annotated

Genes (Rattus norvegicus)
Nr3c1  (nuclear receptor subfamily 3, group C, member 1)
Nr3c1em1Kuan  (nuclear receptor subfamily 3, group C, member 1; CRISPR/Cas9 induced mutant1, Kuan)

Genes (Mus musculus)
Nr3c1  (nuclear receptor subfamily 3, group C, member 1)

Genes (Homo sapiens)
NR3C1  (nuclear receptor subfamily 3 group C member 1)

Strains
SD-Nr3c1em1Kuan  (NA)


Additional Information