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Relevance to Autism

A study indicate a molecular mechanism involving the OPRM1 gene that may play a role in diseases characterized by deficits in attachment behavior, such as autism or reactive attachment disorder (Moles, Kieffer and D'Amato 2004).

Molecular Function

The encoded protein has mu-opioid receptor activity.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Deficit in attachment behavior in mice lacking the mu-opioid receptor gene.
ASD
Support
Integrating de novo and inherited variants in 42
ASD
Support
Mutational Landscape of Autism Spectrum Disorder Brain Tissue
ASD
Highly Cited
A potent and selective endogenous agonist for the mu-opiate receptor.
Recent Recommendation
Autistic-like syndrome in mu opioid receptor null mice is relieved by facilitated mGluR4 activity.
Recent Recommendation
Interactions between CB1 cannabinoid and mu opioid receptors mediating inhibition of neurotransmitter release in rat nucleus accumbens core.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN185R001 
 5_prime_UTR_variant 
 c.-489C>T 
  
 Unknown 
  
  
 GEN185R002 
 missense_variant 
 c.179C>T 
 p.Pro60Leu 
 De novo 
  
 Multiplex 
 GEN185R003 
 missense_variant 
 c.382G>A 
 p.Val128Met 
 De novo 
  
  

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
6
Duplication
 1
 
6
Duplication
 1
 
6
Deletion
 1
 
6
Deletion-Duplication
 7
 
6
Deletion
 4
 
6
Deletion
 3
 

Model Summary

Oprm1 is involved in G-protein coupled receptor activity and voltage-gated calcium channel activity; mice with homozygous null Oprm1 deletion have deficits in sociability and communication;.

References

Type
Title
Author, Year
Primary
Region specific up-regulation of oxytocin receptors in the opioid oprm1 (-/-) mouse model of autism.
Additonal
Early Social Enrichment Improves Social Motivation and Skills in a Monogenic Mouse Model of Autism, the Oprm1 (-/-) Mouse.

M_OPRM1_1_HM_KO

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Oprm1 null mice were generated by disruption of exon 2 in the Oprm1 gene, and housed with their own lactating mother until weaning at P28;.
Allele Type: Targeted
Strain of Origin: Unreported
Genetic Background: C57BL6/J
ES Cell Line: Unreported
Mutant ES Cell Line: Unreported
Model Source: Animal facility at IRCCS Santa Lucia Foundation, Rome, Italy

M_OPRM1_1_HM_KO

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuroreceptor levels: oxt1
Increased
Description: Compared to wildtype controls oprm1 homozygous null mice display increased oxytocin receptor (oxtr) expression selectively in the nucleus accumbens (nacc)
Exp Paradigm: Brain regions were selected on the basis of co-expression of oxtr and mu opioid receptors (mor); nissl staining and acetylcholinesterase (ache) staining was done to identify brain regions; quantitation was based on iodine-125 incorporation;
 Radioligand binding studies
 Adult
Neuroreceptor levels: oxt1
Increased
Description: Compared to wildtype controls oprm1 homozygous null mice display increased oxytocin receptor (oxtr) expression selectively in the medial anterior olfactory nucleus (aon)
Exp Paradigm: Brain regions were selected on the basis of co-expression of oxtr and mu opioid receptors (mor); nissl staining and acetylcholinesterase (ache) staining was done to identify brain regions; quantitation was based on iodine-125 incorporation;
 Radioligand binding studies
 Adult
Neuroreceptor levels: oxt1
Increased
Description: Compared to wildtype controls oprm1 homozygous null mice display increased oxytocin receptor (oxtr) expression in the anterior nuclei of the amygdala (central anygdaloid nucleus- cea and medial amygdaloid nucleus-mea)
Exp Paradigm: Brain regions were selected on the basis of co-expression of oxtr and mu opioid receptors (mor); nissl staining and acetylcholinesterase (ache) staining was done to identify brain regions; quantitation was based on iodine-125 incorporation;
 Radioligand binding studies
 Adult
Social approach2
Decreased
Description: Oprm1 homozygous null mice spent less time close to the conspecific mouse than the object compared to wildtype controls;
Exp Paradigm: Animals tested before weaning; a conspecific nmri mouse, age and sex matched was used as stimulus;
 Three-chamber social approach test
 4-4.2 weeks
Social habituation2
Decreased
Description: Male oprm1 homozygous null mice had reduced capacity in distinguishing an unknown from a familiar mouse compared to wt mice, during serial presentation of the intruder in the resident intruder test
Exp Paradigm: Partners were younger mice, p45-70; 5 consecutive 1 min interaction sessions; the same intruder was used for the first four sessions and an unknown one was used for the 5th session;
 Resident-intruder test
 3-3.6 months
Social approach2
Decreased
Description: Total time spent close to partners was not affected in oprm1 null mice compared to wt mice of either genders; female oprm1 null mice showed similar interest toward their female partners whether the latter were oprm1 null mice or wt mice; male oprm1 null mice showed preference of males of the alien (wt genotype) compared to oprm1 null mice partners whereas wt males showed avoidance of the males of the alien line (oprm1 null mice);
Exp Paradigm: Subject was simultaneously exposed to mice with different genotypes
 Three-chamber social approach test
 3-3.6 months
Social memory2
Decreased
Description: Although a general analysis showed oprm1 homozygous null mice were able to recognize partners' familiarity during repeated exposures according to reduction in time spent investigating the partners during successive sessions, a sex based analysis showed male oprm1 homozygous null mice had significantly reduced capacity in distinguishing an unknown from a familiar mouse compared to wt mice
Exp Paradigm: Partners were younger mice, p45-70; 5 consecutive 1 min interaction sessions; the same intruder was used for the first four sessions and an unknown one was used for the 5th session;
 Resident-intruder test
 3-3.6 months
Social approach1
Decreased
Description: Oprm1 homozygous null mice spent less time close to the conspecific mouse than the object compared to wildtype controls;
Exp Paradigm: Measured following, sniffing nose, body, and ano-genital region of the partner
 Reciprocal social interaction test
 Adult
Social interaction2
Decreased
Description: Male oprm1 homozygous null mice spent less time in social investigation than wt mice;
Exp Paradigm: Partners were younger mice, p45-70; 5 consecutive 1 min interaction sessions; the same intruder was used for the first four sessions and an unknown one was used for the 5th session;
 Resident-intruder test
 3-3.6 months
Ultrasonic vocalization: isolation induced2
Decreased
Description: Oprm1 ko pups reared by their own mother in a clean cage emitted significantly fewer number of ultrasonic vocalizations than wildtype controls in a clean cage with a single mother; there was no effect of sex on ultrasonic emissions; there was no difference between home-cage and clean bedding exposure on oprm1 ko mice;
Exp Paradigm: After 1h acclimatization to the room, mother was removed, pups were left in the home cage; pups (one male and one female) were then placed in a beaker containing bedding from their own cage or clean bedding and vocalizations recorded;
 Monitoring ultrasonic vocalizations
 P8
Ultrasonic vocalization: interaction induced: opposite sex stimulus1
Decreased
Description: During male and female social interaction, oprm1 null males emitted reduced number of ultrasonic vocalizations;
Exp Paradigm: Only male behavior tested, independent of the female receptivity; five minutes after the males intranasal drug/saline administration, a female of the same genotype was introduced into the males home cage and left for 5 min; oprm1 null males were exposed to oprm1 null females and wt males to wt females;
 Monitoring ultrasonic vocalizations
 Adult
Size/growth2
 No change
 Body weight measurement
 P8, 1 month, 2.7 month
Anxiety2
 No change
 Elevated plus maze test
 2.5-3 months
Exploratory activity1
 No change
 Reciprocal social interaction test
 Adult
General locomotor activity1
 No change
 Reciprocal social interaction test
 Adult
Neuroreceptor levels: oxt1
 No change
 Radioligand binding studies
 Adult
Self grooming: social context1
 No change
 Reciprocal social interaction test
 Adult
Social interaction: opposite sex1
 No change
 Reciprocal social interaction test
 Adult
 Not Reported: Circadian sleep/wake cycle, 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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