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Relevance to Autism

CRHR2-deficient mice displayed altered social approach in the social maze test but normal novel object preference; specific knockdown of CRHR2 in the medial amygdala recapitulated this phenotype (Shemesh et al., 2016). In the same report, it was shown that pharmacological activation of CRHR2 in the medial amygdala increased preference for novel mice. Previous studies had shown that mice deficient for CRHR2 displayed anxiety-like behavior and were hypersensitive to stress (Bale et al., 2000; Kishimoto et al., 2000).

Molecular Function

The protein encoded by this gene belongs to the G-protein coupled receptor 2 family, and the subfamily of corticotropin releasing hormone receptor. This receptor shows high affinity for corticotropin releasing hormone (CRH), and also binds CRH-related peptides such as urocortin. CRH is synthesized in the hypothalamus, and plays an important role in coordinating the endocrine, autonomic, and behavioral responses to stress and immune challenge.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Ucn3 and CRF-R2 in the medial amygdala regulate complex social dynamics.
Support
Deletion of crhr2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2.
Support
Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress.
Support
Integrating de novo and inherited variants in 42
ASD
Support
Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
ASD

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN844R001 
 splice_site_variant 
 c.90+1G>A 
  
 Familial 
 Maternal 
 Multiplex (monozygotic twins) 
 GEN844R002 
 missense_variant 
 c.119A>G 
 p.Asp40Gly 
 De novo 
  
 Simplex 

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
7
Duplication
 1
 
7
Deletion
 1
 
7
Duplication
 1
 
7
Duplication
 1
 
7
Deletion
 2
 

Model Summary

Crhr2 null mice have impaired social behavior displaying reduced preference for a novel mouse over a familiar mouse.

References

Type
Title
Author, Year
Primary
Ucn3 and CRF-R2 in the medial amygdala regulate complex social dynamics.

M_CRHR2_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Crhr2 is knocked ou in germline. Details of the construct are not provided in Shemesh et al (PMID 27428651).
Allele Type: Targeted(knockout)
Strain of Origin:
Genetic Background: C57Bl/6*129
ES Cell Line:
Mutant ES Cell Line:
Model Source: C57Bl/6*129

M_CRHR2_2_KD_MEA

Model Type: Genetic
Model Genotype: Homozygous
Mutation: A lentivirus encoding a shRNA targeting the Crhr2 transcript was bilaterally injected into the medial amygdala of adult mice. Mice were tested 10 days after the injection.
Allele Type: Targeted(knockdown)
Strain of Origin:
Genetic Background:
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_CRHR2_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Social memory1
Decreased
Description: Crhr2 null mice have no preference for a novel mouse over a familiar mouse and spend increased time interacting with the familiar mouse compared to wildtype. authors indicate the role of ucn3 in modulating interaction with familiar conspecifics
Exp Paradigm: NA
 Three-chamber social approach test
 9-11 weeks
Exploratory activity1
 No change
 Three-chamber social approach test
 9-11 weeks
Object recognition memory1
 No change
 Novel object recognition test
 9-11 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory

M_CRHR2_2_KD_MEA

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Social memory1
Decreased
Description: Knockdown of crhr2 specifically in the amygdala also results in impaired social memory, these mice do not display preference for novel mice and show increased preference towards familiar mice unlike controls injected with artificial cerebrospinal fluid, indicating a specific role of the amygdalar crhr2 in this impairment
Exp Paradigm: NA
 Three-chamber social approach test
 9-11 weeks
Anxiety1
 No change
 Light-dark exploration test
 9-11 weeks
Anxiety1
 No change
 Open field test
 9-11 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory

 

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