This gene was identified in an ASD whole-exome sequencing study and subsequent TADA (transmission and de novo association) analysis as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (De Rubeis et al., 2014).
Molecular Function
This gene encodes the mineralocorticoid receptor, which mediates aldosterone actions on salt and water balance within restricted target cells. The protein functions as a ligand-dependent transcription factor that binds to mineralocorticoid response elements in order to transactivate target genes. Mutations in this gene cause autosomal dominant pseudohypoaldosteronism type I, a disorder characterized by urinary salt wasting. Defects in this gene are also associated with early onset hypertension with severe exacerbation in pregnancy.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Synaptic, transcriptional and chromatin genes disrupted in autism.
The mutant mice show impaired learning of the water-maze task and deficits in measures of working memory on the radial maze due to behavioral perseverance and stereotypy.
References
Type
Title
Author, Year
Primary
Loss of the limbic mineralocorticoid receptor impairs behavioral plasticity.
Model Type:
Genetic
Model Genotype:
Homozygous flox; Heterozygous Cre
Mutation:
Conditional deletion of exon 3 of the Nr3c2 gene using CamkII-cre, in excitatory neurons of the forebrain
Allele Type: Conditional loss-of-function
Strain of Origin: 129Ola x FVB/N
Genetic Background: C57Bl/6J
ES Cell Line: 129Ola
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
CaMKIIa-HA-NR3C2 (human).
Allele Type: Transgenic
Strain of Origin: C57Bl/6J CBA
Genetic Background: ES Cell Line: C57Bl/6J CBA
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Description: Aberrant layout of the mossy fibers compared to control
Exp Paradigm: Histology: nissl analysis of the projection of granule cell axons to the ca3 field of the hippocampus
Description: Increased perseveration in place navigation in reversal task of water maze, and reentry of arms in radial arm maze
Exp Paradigm: Morris water maze test; eight-arm radial maze test: factor analysis of behavioral variables- eight-arm radial maze test
Description: Increased perseveration in place navigation in reversal task of water maze, and reentry of arms in radial arm maze
Exp Paradigm: Morris water maze test; eight-arm radial maze test: factor analysis of behavioral variables-morris water maze test
Description: Decreased exploratory behavior measured by a longer latency to leave the center of the board compared to nr3c2_2_tg, which show no change compared to nr3c2_1_cko_camk-cre-littermate controls
Exp Paradigm: Barnes maze test: 12-hole free exploration trial
Description: Impaired short-term spatial memory measured by decreased time spent in the quadrant of previous exit trial
Exp Paradigm: Barnes maze test: 12-hole stimulus-response task, exit hole is marked by a visual cue (stimulus) and changes every trial, 6 trials per day over 2 days
Description: Impaired performance in spatial learning compared to littermate controls, needed more time to find the exit hole
Exp Paradigm: Barnes maze test: 12-hole spatial task, exit hole is determined by extra-maze spatial cues, 6 trials over one day
Description: Impaired learning of stimulus-response task, significantly on day 2
Exp Paradigm: Barnes maze test: 12-hole stimulus-response task, exit hole is marked by a visual cue (stimulus) and changes every trial, 6 trials per day over 2 days
Description: Impaired performance judged by number of decreased number of correct choices in first eight arm visits and increased reentry errors
Exp Paradigm: Eight-arm radial maze test - baited arms
Description: Deficit in acquisition (increased latency to platform across trials), reduced swim speed and an increased use of inappropriate strategies, such as passive floating and aimless swimming
Exp Paradigm: Morris water maze test - 18 trials for a first platform location (place acquisition)
Description: Impaired learning of stimulus-response task, significantly on day 2
Exp Paradigm: Barnes maze test: 12-hole stimulus-response task, exit hole is marked by a visual cue (stimulus) and changes every trial, 6 trials per day over 2 days
Description: Decreased memory, shown by increased latency to reach quadrant of spatial exit and reduced time in this quadrant
Exp Paradigm: Barnes maze test: 12-hole stimulus-response task, trial one 7 days after spatial task
Description: Inferior performance compared to controls
Exp Paradigm: Morris water maze test - 12 trials with a new platform location in the opposite quadrant (place reversal)
Description: Impaired short-term spatial memory measured by decreased time spent in the quadrant of previous exit trial, and increased latency to previous exit trial
Exp Paradigm: Barnes maze test: 12-hole stimulus-response task, exit hole is marked by a visual cue (stimulus) and changes every trial, 6 trials per day over 2 days
Description: Decreased memory, shown by increased latency to reach quadrant of spatial exit and reduced time in this quadrant
Exp Paradigm: Barnes maze test: 12-hole stimulus-response task, trial one 7 days after spatial task
Description: Upregulation of gr in the cornu ammonis compared to controls, while in the pvn which does not express mr normally does not show a change in gr expression
Exp Paradigm: Immunohistochemistry: gr
Description: Enhanced performance in spatial learning compared to littermate controls
Exp Paradigm: Barnes maze test: 12-hole spatial task, exit hole is determined by extra-maze spatial cues, 6 trials over one day
