A number of studies have focused on the genetic association of the OXTR gene with autism, including negative association. Cohorts and populations that have shown positive associations include AGRE, Chinese Han, Caucasian, Japanese, Irish, Portuguese, US and the United Kingdom. In addition, one study (Gregory et al., 2009) found a rare deletion in the OXTR gene in an autistic family. Genetic association has also been found between OXTR and lower levels of difficulty hearing and understanding people in noisy environments (Tops et al., 2011).
Molecular Function
The protein encoded by this gene belongs to the G-protein coupled receptor family and acts as a receptor for oxytocin. Its activity is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population.
Meta-analysis of 2984 ASD families and 280 cases/440 controls from 6 independent samples (from Liu et al., 2010a; Tansey et al., 2010; and Campbell et al., 2011)
Meta-analysis of 2984 ASD families and 280 cases/440 controls from 6 independent samples (from Liu et al., 2010a; Tansey et al., 2010; and Campbell et al., 2011)
Meta-analysis of 2900 ASD families and 280 cases/440 controls from 6 independent samples (from Wu et al., 2005; Jacob et al., 2007; Liu et al., 2010; Wermter et al., 2010; and Campbell et al., 2011)
Homberg sample of 178 cases: 135 complete parent-offspring trios, 29 parent child duos; 89% Male; 72.8% high-functioning ASD (IQ70). Meta-analysis sample: two previously published studies (Tansey et al., 2010; Campbell et al., 2011) and two previously unpublished German cohorts from PMID 26788924
207 families with an ASD proband (diagnosed using ADOS, ADI-R, and confirmed according to DSM-IV-TR) recruited through the Developmental Disorders Clinic of the University of Chicago (UIC) Institute of Juvenile Research
207 families with an ASD proband (diagnosed using ADOS, ADI-R, and confirmed according to DSM-IV-TR) recruited through the Developmental Disorders Clinic of the University of Chicago (UIC) Institute of Juvenile Research
207 families with an ASD proband (diagnosed using ADOS, ADI-R, and confirmed according to DSM-IV-TR) recruited through the Developmental Disorders Clinic of the University of Chicago (UIC) Institute of Juvenile Research
207 families with an ASD proband (diagnosed using ADOS, ADI-R, and confirmed according to DSM-IV-TR) recruited through the Developmental Disorders Clinic of the University of Chicago (UIC) Institute of Juvenile Research
207 families with an ASD proband (diagnosed using ADOS, ADI-R, and confirmed according to DSM-IV-TR) recruited through the Developmental Disorders Clinic of the University of Chicago (UIC) Institute of Juvenile Research
Cohort of 341 ASD probands (mean age 10.6 years) consisting of 211 Caucasian probands (mean age 11.3 3.8 years, 22.8% female) and 130 non-Caucasian probands (mean age 9.8 4.0 years, 19.2% female)
OXTR plays a critical role in regulating several aspects of social behavior and may have important implications for developmental psychiatric disorders characterized by deficits in social behavior.
References
Type
Title
Author, Year
Primary
Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A targeting vector with PGK-Neo cassette inserted into intron 3 along with three loxP sites around exons 2 and 3 and the PGK-Neo.
Allele Type: Targeted (knock-out)
Strain of Origin: 129P2/OlaHsd
Genetic Background: 129P2/OlaHsd * C57BL/6J
ES Cell Line: E14TG2a
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Cre-loxP mediated deletion of exon 2 and 3 of Oxtr gene with Cre recombinase under the control of a germ cell expression promoter.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: 129/Sv R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 2 - 3 of the Oxtr gene using CamkII-cre, in excitatory neurons of the forebrain
Allele Type: Conditional loss-of-function
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: 129/Sv R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Gene targeted disruption of Exons 3 and 4 of the Oxtr gene.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not Specified
Genetic Background: 129/Ola x C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
A targeting vector with PGK-Neo cassette inserted into intron 3 along with three loxP sites around exons 2 and 3 and the PGK-Neo.
Allele Type: Targeted (knock-out)
Strain of Origin: Not Specified
Genetic Background: B6.129SJ-Oxtrtm1.1Wsy/J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 2-3 of the OXTR gene using a cre expressing AAV vector stereotaxically injected into the ventral subiculum (VnSb), ablating postsynaptic oxytocin receptors in the region
Allele Type: Conditional loss-of-function
Strain of Origin: Genetic Background: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL
ES Cell Line: 129/Sv R1 line
Mutant ES Cell Line: Model Source: JAX
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 2-3 of the OXTR gene using a cre expressing AAV vector stereotaxically injected into the Dorsal Raphe Nucleus (DrRN),ablating postsynaptic oxytocin receptors in the region
Allele Type: Conditional loss-of-function
Strain of Origin: Genetic Background: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL
ES Cell Line: 129/Sv R1 line
Mutant ES Cell Line: Model Source: JAX
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Male wild type mice were injected with the Oxytocin Receptor Antagonist - L-368,899 hydrocholoride, 5 mg/kg twice a day for two days, intraperitoneally or using Andalman probes.
Allele Type: NA
Strain of Origin: Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: JAX
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 2-3 of the OXTR gene using a cre expressing AAV vector stereotaxically injected into the nucleus accumbens (Nac), ablating postsynaptic oxytocin receptors in the region
Allele Type: Conditional loss-of-function
Strain of Origin: Genetic Background: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL
ES Cell Line: 129/Sv R1 line
Mutant ES Cell Line: Model Source: JAX
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 2-3 of the OXTR gene using a cre expressing rabies viral vector stereotaxically injected into the nucleus accumbens (Nac), ablating the presynaptic oxytocin receptors
Allele Type: Conditional loss-of-function
Strain of Origin: Genetic Background: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL
ES Cell Line: 129/Sv R1 line
Mutant ES Cell Line: Model Source: JAX
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 2-3 of the OXTR gene using a cre expressing AAV vector stereotaxically injected into the anterior cingulate cortex (ACC), ablating postsynaptic oxytocin receptors in the region
Allele Type: Conditional loss-of-function
Strain of Origin: Genetic Background: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * SJL
ES Cell Line: 129/Sv R1 line
Mutant ES Cell Line: Model Source: JAX
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
DA-Oxtr homozygous conditional knockout mice (DAT-cre, Oxtr^fl/fl) mice were generated by crossing DAT-cre mice ( JAX, cat no. 020080) to Oxtr^fl/fl mice (from Benjamin R. Arenkiel's laboratory, PMID 18356275) and cohoused by genotype and sex.
Allele Type: Conditional knockout
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: JAX
Model Type:
RESCUE-Microbiome
Model Genotype:
Homozygous
Mutation:
Mice with selective ablation of oxytocin receptor in dopaminergic neurons were treated with either vehicle or L. reuteri, added daily in drinking water for 4 weeks.
Allele Type: Conditional knockout
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: JAX
Description: Increased incidence of ptz induced myoclonic seizures with reduced time latency
Exp Paradigm: Male mice: eeg recordings after 30 mg/kg ptz administration
Description: Decreased social interactions indicated by no change in time spent at cage occupied by unfamiliar mouse vs. empty cage
Exp Paradigm: Male mice: sociabliity and preference for social novelty test
Description: Increased aggression as measured by number of attacks and attack and rattle latency
Exp Paradigm: Male mice: observation of aggressoin against opponent mouse
Description: Decreased social memory indicated by same duration spent with stranger and the familiar mouse
Exp Paradigm: Male mice: sociabliity and preference for social novelty test
Description: Decreased cognitive flexibility indicated by slower reversal learning of baited arm
Exp Paradigm: Male mice: appetite-motivated t-maze test
Description: Decreased social interaction indicated by decreased frontal approach, flight, and chase/follow behavior
Exp Paradigm: Visual burrowing system - measures for frontal approach, flight, and chase/follow
Description: Decreased social approach indicated by no significant preference for one side over the other and significant reduction in the frequency of sniff behavior
Exp Paradigm: Three-chambered social approach test
Description: Injection of aav-cre-egfp to delete otrs from cells within the dorsal raphe nucleus, an important source of serotonin in the brain, prevented social conditioning in the social cpp testlearning in wild type or conditional otr ko mice
Exp Paradigm: The protocol involved two days of conditioning. mice were housed in home cages, containing 3-5 cage-mates, onto corn cob bedding. animals were placed in an open field chamber with infrared beams. the apparatus was divided into two equally sized zones using a clear plastic wall, with a circular opening at the base. during preconditioning the baseline preference for the two sets of bedding was established. during social conditioning mice were housed with cage mates on one type of bedding for 24 hrs (social bedding cue) and then on the other type of bedding in the next 24 hrs (isolated bedding cue- conditioning). 24 hrs later in the post conditioning trial, the preference of the mice for social versus isolate cues was established in the open field chamber, in
Description: Otr-antagonist treated mice showed no preference to socially conditioned context, whereas wild type mice showed robust preference to it.
Exp Paradigm: The protocol involved two days of conditioning. mice were housed in home cages, containing 3-5 cage-mates, onto corn cob bedding. animals were placed in an open field chamber with infrared beams. the apparatus was divided into two equally sized zones using a clear plastic wall, with a circular opening at the base. during preconditioning the baseline preference for the two sets of bedding was established. during social conditioning mice were housed with cage mates on one type of bedding for 24 hrs (social bedding cue) and then on the other type of bedding in the next 24 hrs (isolated bedding cue- conditioning). 24 hrs later in the post conditioning trial, the preference of the mice for social versus isolate cues was established in the open field chamber, in
Description: OTR-antagonist treated mice showed no preference to socially conditioned context, whereas wild type mice showed robust preference to it.
Exp Paradigm: The protocol involved two days of conditioning. Mice were housed in home cages, containing 3-5 cage-mates, onto corn cob bedding. Animals were placed in an open field chamber with infrared beams. The apparatus was divided into two equally sized zones using a clear plastic wall, with a circular opening at the base. During preconditioning the baseline preference for the two sets of bedding was established. During social conditioning mice were housed with cage mates on one type of bedding for 24 hrs (social bedding cue) and then on the other type of bedding in the next 24 hrs (isolated bedding cue- conditioning). 24 hrs later in the post conditioning trial, the preference of the mice for social versus isolate cues was established in the open field chamber, in
Description: Injection of rbv-cre-egfp to delete presynaptic otrs in the nucleus accumbens blocked social cpp in conditional otr ko mice, but had no effect on wild type mice
Exp Paradigm: The protocol involved two days of conditioning. mice were housed in home cages, containing 3-5 cage-mates, onto corn cob bedding. animals were placed in an open field chamber with infrared beams. the apparatus was divided into two equally sized zones using a clear plastic wall, with a circular opening at the base. during preconditioning the baseline preference for the two sets of bedding was established. during social conditioning mice were housed with cage mates on one type of bedding for 24 hrs (social bedding cue) and then on the other type of bedding in the next 24 hrs (isolated bedding cue- conditioning). 24 hrs later in the post conditioning trial, the preference of the mice for social versus isolate cues was established in the open field chamber, in
Description: Mutants show decrease in ampar/nmdar ratio in the da neurons in the vta compared with controls, indicating a decrease in ltp.
Exp Paradigm: NA
Description: Lactobacillus reuteri treatment does not increase social interaction evoked ampar/nmdar ratio in vta da neurons in mutants.
Exp Paradigm: NA
