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Relevance to Autism

A de novo in-frame deletion variant in the GRM5 gene was identified by exome sequencing in an ASD case from the Simons Simplex Collection (Iossifov et al., 2012). Twelve rare variants in the GRM5 gene were identified in a cohort of 290 non-syndromic ASD cases that were not observed in 300 ethnically matched controls in a subsequent study (Kelleher III et al., 2012).

Molecular Function

Receptor for glutamate. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
De novo gene disruptions in children on the autistic spectrum.
ASD
Positive Association
Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder.
ADHD
Support
Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes.
ASD
Support
High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism.
Non-syndromic ASD
Support
Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy.
Epilepsy
Recent Recommendation
Decreased expression of mGluR5 within the dorsolateral prefrontal cortex in autism and increased microglial number in mGluR5 knockout mice: Pathoph...
ASD

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN355R001 
 inframe_deletion 
 delTCT 
 679/1181;679/1213 
 De novo 
  
 Simplex 
 GEN355R002 
 synonymous_variant 
 c.87T>C 
 p.(=) 
  
  
 Multiplex 
 GEN355R003 
 missense_variant 
 c.727G>T 
 p.Ala243Ser 
  
  
 Multiplex 
 GEN355R004 
 synonymous_variant 
 c.846G>A 
 p.(=) 
  
  
 Multiplex 
 GEN355R005 
 intron_variant 
 c.911+3G>A 
  
  
  
 Multiplex 
 GEN355R006 
 synonymous_variant 
 c.1167A>G 
 p.(=) 
  
  
 Multiplex 
 GEN355R007 
 missense_variant 
 c.1417G>C 
 p.Glu473Gln 
  
  
 Multiplex 
 GEN355R008 
 synonymous_variant 
 c.2127T>A 
 p.(=) 
  
  
 Multiplex 
 GEN355R009 
 synonymous_variant 
 c.2379T>C 
 p.(=) 
  
  
 Multiplex 
 GEN355R010 
 intron_variant 
 c.2630+10G>A 
  
  
  
 Multiplex 
 GEN355R011 
 synonymous_variant 
 c.2652G>A 
 p.(=) 
  
  
 Multiplex 
 GEN355R012 
 synonymous_variant 
 c.3123C>T 
 p.(=) 
  
  
 Multiplex 
 GEN355R013 
 missense_variant 
 c.3503T>C 
 p.Leu1168Pro 
  
  
 Multiplex 
 GEN355R014 
 synonymous_variant 
 c.381A>G 
 p.(=) 
 Unknown 
  
 Unknown 
 GEN355R015 
 synonymous_variant 
 c.657A>C 
 p.(=) 
 Unknown 
  
 Unknown 
 GEN355R016 
 synonymous_variant 
 c.1206C>T 
 p.(=) 
 Unknown 
  
 Unknown 
 GEN355R017 
 missense_variant 
 c.5T>C 
 p.Val2Ala 
 Unknown 
  
 Unknown 
 GEN355R018 
 missense_variant 
 c.412C>T 
 p.Arg138Cys 
 Unknown 
  
 Unknown 
 GEN355R019 
 missense_variant 
 c.1358C>T 
 p.Thr453Met 
 Unknown 
  
 Unknown 
 GEN355R020 
 missense_variant 
 c.1949G>A 
 p.Gly650Asp 
 Unknown 
  
 Unknown 
 GEN355R021 
 missense_variant 
 c.523A>G 
 p.Thr175Ala 
 De novo 
  
 Simplex 

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN355C001 
 copy_number_loss 
  
  
  
 Discovery: 1013 European ADHD cases from CHOP, 4105 healthy European controls; Replication: 2493 cases, 9222 controls 
 Discovery & Replication 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
11
Duplication
 1
 
11
Deletion
 1
 
11
Deletion
 1
 
11
Deletion-Duplication
 10
 
11
Deletion
 2
 
11
Deletion-Duplication
 9
 

Model Summary

Grm5 null mice display impaired synaptic plasticity.

References

Type
Title
Author, Year
Additional
mGluR5 ablation in cortical glutamatergic neurons increases novelty-induced locomotion.
Additional
Disruption of mGluR5 in parvalbumin-positive interneurons induces core features of neurodevelopmental disorders.
Primary
Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP.

M_GRM5_3_CKO_HM

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Conditional deletion of exon 7 of Grm5 using Nex-cre, in excitatory neurons. Resulting mice had 40% reduction in GRM5 production in the cortex of adult mice, these mice were on a mixed background of 129 SVJ and C57BL/6
Allele Type: Conditional loss-of-function
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
ES Cell Line: R1
Mutant ES Cell Line:
Model Source:

M_GRM5_3_CKO_HM_ Methylphenidate

Model Type: Pharmaceutical intervention
Model Genotype: Hemizygous
Mutation: Grm5 conditional knockout mice with loss of Grm5 from excitatory (glutamatergic) neurons, were injected with Methylphenidate (Ritalin) at a dose of 8mg/kg i.p.
Allele Type: Conditional loss-of-function
Strain of Origin:
Genetic Background: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_GRM5_3_CKO_HM_ MPEP

Model Type: Pharmaceutical intervention
Model Genotype: Hemizygous
Mutation: Grm5 conditional knockout mice with loss of Grm5 from excitatory (glutamatergic) neurons,were injected with MPEP at a dose of 40 mg/kg i.p.
Allele Type: Conditional loss-of-function
Strain of Origin:
Genetic Background: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_GRM5_4_CKO_HM

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Conditional deletion of exon 7 of Grm5 using Nex-cre, in excitatory neurons. Nex-Cre/+ mice and Grm5 f/f mice were backcrossed, separately, to C57BL/6 background for 5 and 8 generations
Allele Type: Conditional loss-of-function
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: C57BL/6
ES Cell Line: R1
Mutant ES Cell Line:
Model Source:

M_GRM5_6_CKO_HM_PvalbN

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Conditional deletion of exon 7 of Grm5 using Pvalb-cre in parvalbumin expressing interneurons starting at postnatal week 2 and by week 12 only 18% of the original cells co-expressing PV and Grm5 continue to do so
Allele Type: Conditional loss-of-function
Strain of Origin:
Genetic Background: 129Svj *C57Bl/6
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_GRM5_6_CKO_HM_PvalbN_Amphetamine

Model Type: Pharmaceutical intervention
Model Genotype: Homozygous
Mutation: Parvalbumin neuron specific Grm5 conditional knockout mice were treated with amphetamine at 2mg/kg (i.p.) to activate the dopaminergic system, treatment with amphetamine also usually leads to hyperactivity in wild type mice
Allele Type: Conditional loss-of-function
Strain of Origin:
Genetic Background: 129Svj *C57Bl/6
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_GRM5_6_CKO_HM_PvalbN_PCP-1

Model Type: Pharmaceutical intervention
Model Genotype: Homozygous
Mutation: Parvalbumin neuron specific Grm5 conditional knockout mice were treated with phenylcyclidine(PCP) at 1 mg/kg (i.p.) to activate the dopaminergic system, treatment with PCP usually leads to hyperactivity in wild type mice
Allele Type: Conditional loss-of-function
Strain of Origin:
Genetic Background: 129Svj *C57Bl/6
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_GRM5_6_CKO_HM_PvalbN_PCP-2

Model Type: Pharmaceutical intervention
Model Genotype: Homozygous
Mutation: Parvalbumin neuron specific Grm5 conditional knockout mice were treated with phenylcyclidine(PCP) at 2.5 mg/kg (i.p.) to activate the dopaminergic system, treatment with PCP usually leads to hyperactivity in wild type mice
Allele Type: Conditional loss-of-function
Strain of Origin:
Genetic Background: 129Svj *C57Bl/6
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_GRM5_6_CKO_HM_PvalbN_PCP-3

Model Type: Pharmaceutical intervention
Model Genotype: Homozygous
Mutation: Parvalbumin neuron specific Grm5 conditional knockout mice were treated with phenylcyclidine(PCP) at 5 mg/kg (i.p.) to activate the dopaminergic system, treatment with PCP usually leads to hyperactivity in wild type mice.
Allele Type: Conditional loss-of-function
Strain of Origin:
Genetic Background: 129Svj *C57Bl/6
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_GRM5_6_CKO_HM_PvalbN_PCP-4

Model Type: Pharmaceutical intervention
Model Genotype: Homozygous
Mutation: Parvalbumin neuron specific Grm5 conditional knockout mice were treated with phenylcyclidine(PCP) at 10 mg/kg (i.p.) to activate the dopaminergic system, treatment with PCP usually leads to hyperactivity in wild type mice.
Allele Type: Conditional loss-of-function
Strain of Origin:
Genetic Background: 129Svj *C57Bl/6
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_Grm5_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: A targeting vector was designed to delete a 0.4 kb fragment containing part of exon 1 and a part of intron 1, with a neomycin resistance cassette. F2 Hets were crossed with each other to provide the homozygotes.
Allele Type: Targeted (knock-out)
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: 129S1/Sv * 129X1/SvJ * CD-1
ES Cell Line: R1
Mutant ES Cell Line:
Model Source:

M_Grm5_2_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: A targeting vector was designed to delete a 0.4 kb fragment containing part of exon 1 and a part of intron 1, with a neomycin resistance cassette.
Allele Type: Targeted (knock-out)
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: 129S1/Sv * 129X1/SvJ * CD-1
ES Cell Line: R1
Mutant ES Cell Line:
Model Source:

M_GRM5_3_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hyperactivity1
Increased
Description: Grm5 CNKO mice show hyperactivity in the open field test in total distance traveled, movement time and average horizontal speed or vertical rearing.
Exp Paradigm: Activity measured in the novel open field environment
 Open field test
 Unreported
Synaptic plasticity1
Decreased
Description: Grm5 CNKO mice have reduced cannabinoid receptor 1 dependent LTD in the prefrontal cortex
Exp Paradigm: FEPSPs were recorded in the prelimbic layer V/VI while stimulating in layer II/III in the presence of GABA-A antagonist
 Field potential recordings: long-term depression (LTD)
 Unreported
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 Unreported
Sensorimotor gating1
 No Change
 Prepulse inhibition
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / Ultrastructure / Cytoarchitecture, Repetitive behavior, Seizure, Social behavior

M_GRM5_3_CKO_HM_ Methylphenidate

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hyperactivity1
Increased
Description: Grm5CNKO mice show exacerbated hyper locomotion on treatment with methylphenidate (Ritalin) showing increase in distance traveled, stereotypic activity and vertical activity, compared to littermate controls that are also treated with Ritalin.
 Open field test
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior

M_GRM5_3_CKO_HM_ MPEP

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hyperactivity1
Increased
Description: Grm5 CNKO mice show a greater increase in activity after MPEP compared to control littermates, showing that Grm5 signaling in cortical glutamatergic neurons does not mediate the hyper-kinetc effect of MPEP
 Open field test
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior

M_GRM5_4_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hyperactivity1
Increased
Description: B6-GrmCNKO mice show increased activity in a novel environment similar to mixed background Grm5CNKO
 Open field test
 Unreported
Repetitive digging1
Abnormal
Description: B6-GrmCNKO MALE mice show reduced marble burying activity, however females are same as wild type controls
Exp Paradigm: No. o f marbles being buried
 Marble-burying test
 Unreported
Response to novelty1
Increased
Description: GRM5 KO mice show increased response to novelty or novel environment by increasing locomotor activity
 Open field test
 Unreported
Locomotor activity in diurnal cycle1
 No Change
 Home cage behavior
 Unreported
Anxiety1
 No Change
 Elevated plus maze test
 Unreported
Cued or contextual fear conditioning1
 No Change
 Fear conditioning test: contextual and acoustic cue-dependent
 Unreported
Hormone levels1
 No Change
 
 Unreported
Sensorimotor gating1
 No Change
 Prepulse inhibition
 Unreported
Social approach1
 No Change
 Three-chamber social approach test
 Unreported
Social interaction1
 No Change
 Light-dark exploration test: Light-dark exploration test
 Unreported
 Not Reported: Communications, Developmental profile, Homeostasis, Immune response, Maternal behavior, Molecular profile, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Seizure

M_GRM5_6_CKO_HM_PvalbN

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synapse density: Inhibitory1
Decreased
Description: A significant reduction in inhibitory synapses or contacts between putative pyramidal neurons in the hippocampal CA1 and CA3
 Immunohistochemistry
 4 weeks
Neuronal number: Interneurons1
Decreased
Description: GRM5-PVN cKO mice have a reduction in total number of interneurons expressing parvalbumin in the prelimbic cortex, caudate putamen and CA3 region of the hippocampus
Exp Paradigm: Males only
 Immunohistochemistry: prelimbic cortex, caudate putamen and dorsal hippocampus
 
Event related oscillations (EROs) in electroencephalography (EEG)1
Increased
Description: Grm5-PVN cKO mice have increase in stimulus-induced power gain in the gamma band in the parietal and frontal brain regions
 Electrocorticogram (ECoG): auditory stimulus
 4-7 months
Miniature post synaptic current frequency: inhibitory1
Decreased
Description: 
 Whole-cell patch clamp
 7-9 weeks
Event related potential (ERP) in electroencephalography (EEG)1
Increased
Description: Auditory ERPs in Grm5-PVN KO mice had specific alterations in grand averages of individual components, with increased amplitude at 20-200ms post-stimulus
 Electrocorticogram (ECoG): auditory stimulus
 4-7 months
Event related potential (ERP) in electroencephalography (EEG)1
Decreased
Description: Auditory ERPs in Grm5-PVN cKO mice had specific alterations in grand averages of individual components, with decreased amplitude at 40 ms
 Electrocorticogram (ECoG): auditory stimulus
 4-7 months
Perseveration1
Increased
Description: GRM5-PVN cKO mice have increased perseverative behavior in several behavioral tasks including the Barnes maze test and in the three-chamber social approach test, profound in males
Exp Paradigm: Males only- Three-chamber social approach test
 Three-chamber social approach test
 8-12 weeks
Repetitive digging1
Increased
Description: GRM4-PVN cKO mice bury more marbles in the marble - burying task compared to wild type controls
 Marble-burying test
 8-12 weeks
Perseveration1
Increased
Description: GRM5-PVN cKO mice have increased perseverative behavior in several behavioral tasks including the Barnes maze test and in the three-chamber social approach test, profound in males
Exp Paradigm: Males only-Barnes maze test
 Barnes maze test
 8-12 weeks
Sensorimotor gating1
Increased
Description: Prepulse inhibition ratio is significantly increased in magnitude in GRM5-PVN cKO compared to wild type independent of the startle magnitude, this was corroborated with electromyography recordings conducted in combination to PPI
Exp Paradigm:  Electromyography (EMG)
 Electromyogram (EMG)
 8-12 weeks
Sensorimotor gating1
Increased
Description: Prepulse inhibition ratio is significantly increased in magnitude in GRM5-PVN cKO compared to wild type independent of the startle magnitude, this was corroborated with electromyography recordings conducted in combination to PPI
Exp Paradigm: Prepulse inhibition
 Prepulse inhibition
 8-12 weeks
Social memory1
Decreased
Description: GRM5-PVN cKO mice show no preference or discrimination for novel stimulus mouse over familiar mouse
 Three-chamber social approach test
 8-12 weeks
Self grooming: social context1
Increased
Description: GRM5-PVN cKO display increased self grooming in the three chamber social approach test
 Three-chamber social approach test
 8-12 weeks
Object recognition memory1
Decreased
Description: GRM5-PVN cKO mice have reduced discrimination index for the novel object
 Novel object recognition test
 8-12 weeks
Targeted expression1
Decreased
Description: GRM5 protein expression is significantly reduced in the parvalbumin positive neurons in these cKO mice, there is loss of GRM5 in 82% of cells that express PV and Grm5 in WT
 
 
Anxiety1
 No Change
 Light-dark exploration test: Light-dark exploration test
 8-12 weeks
Spatial learning1
 No Change
 Barnes maze test
 8-12 weeks
Spatial reference memory1
 No Change
 Barnes maze test
 8-12 weeks
Miniature post synaptic current amplitude: inhibitory1
 No Change
 Whole-cell patch clamp
 7-9 weeks
Presynaptic function: paired-pulse facilitation1
 No Change
 Paired-pulse ratio
 7-9 weeks
Synaptic plasticity: hippocampal LTD1
 No Change
 Field potential recordings: long-term depression (LTD): low-frequency stimulation (LFS)
 4 - 11 week
Synaptic plasticity: hippocampal LTP1
 No Change
 Field potential recordings: long-term potentiation (LTP): theta burst stimulation (TBS)
 4 - 11 week
Synaptic plasticity: hippocampal LTP1
 No Change
 Field potential recordings: long-term potentiation (LTP): high-frequency stimulation (HFS)
 4 - 11 week
Social approach1
 No Change
 Three-chamber social approach test
 8-12 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Maternal behavior, Motor phenotype, Seizure

M_GRM5_6_CKO_HM_PvalbN_Amphetamine

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hyperactivity1
Increased
Description: Treatment with amphetamine at 2mg/kg increases activity in GRM5-PVN cKO to levels more than seen in wild type controls treated with amphetamine
 Open field test
 8-12 weeks
Sensorimotor gating1
Increased
Description: Prepulse inhibition ratio remains significantly increased in magnitude in GRM5-PVN cKO compared to wild type after treatment with 2mg/kg of amphetamine
 Prepulse inhibition
 8-12 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Social behavior

M_GRM5_6_CKO_HM_PvalbN_PCP-1

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hyperactivity1
Decreased
Description: Treatment with PCP at 1 mg/kg did not cause similar levels of increase in activity (hyperactivity) in GRM5-PVN cKO compared to similarly treated wild type controls
 Open field test
 8-12 weeks
Sensorimotor gating1
 No Change
 Prepulse inhibition
 8-12 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Social behavior

M_GRM5_6_CKO_HM_PvalbN_PCP-2

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Sensorimotor gating1
Increased
Description: Prepulse inhibition ratio remains significantly increased in magnitude in GRM5-PVN cKO compared to wild type after treatment with 2.5 mg/kg of PCP
 Prepulse inhibition
 8-12 weeks
Hyperactivity1
 No Change
 Open field test
 8-12 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Social behavior

M_GRM5_6_CKO_HM_PvalbN_PCP-3

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Sensorimotor gating1
Increased
Description: Prepulse inhibition ratio remains significantly increased in magnitude in GRM5-PVN cKO compared to wild type after treatment with 5mg/kg of PCP
 Prepulse inhibition
 8-12 weeks
Hyperactivity1
 No Change
 Open field test
 8-12 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Social behavior

M_GRM5_6_CKO_HM_PvalbN_PCP-4

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Sensorimotor gating1
Increased
Description: Prepulse inhibition ratio remains significantly increased in magnitude in GRM5-PVN cKO compared to wild type after treatment with 10mg/kg of PCP
 Prepulse inhibition
 8-12 weeks
Hyperactivity1
 No Change
 Open field test
 8-12 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Social behavior

M_Grm5_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synaptic plasticity1
Decreased
Description: Grm5 null mice have reduced NMDA channel currents receptor mediated long term potentiation in the CA1 region of the hippocampus compared to wild type controls
Exp Paradigm: NMDA receptor mediated channel current was measured as the ratio to the non NMDA component in acute slices of the hippocampus. LTP was induced by four trains of tetani
 Field potential recordings: epsp
 7-8.5 weeks
Synaptic plasticity1
Decreased
Description: A significant reduction in LTP was also seen in the medial perforant pathway of the dentate gyrus of the hippocampus in the Grm5 null mice compared to wild type controls
 Field potential recordings: epsp
 7-8.5 weeks
Cued or contextual fear conditioning: Memory of cue1
Abnormal
Description: Grm5 mice had normal freezing response to shock during traning. However Grm5 null mice show a significant reduction in freezing time in the context where they were trained to receive the shock. They freeze similar to control mice in response to tone CS.
Exp Paradigm: Contextual fear conditioning
 Fear conditioning test: contextual and acoustic cue-dependent
 7-8.5 weeks
Spatial reference memory1
Decreased
Description: Grm5 null mice spend less time exploring the quadrant in which the platform was kep during the training period, unlike wild type mice.
Exp Paradigm: Probe trial
 Morris water maze test
 7-8.5 weeks
Spatial learning1
Decreased
Description: Grm5 null mice had significantly impaired learning in the training days of the hidden platform test in the Morris water maze. They displayed significantly longer latencies in finding the platform.
Exp Paradigm: Hidden platform test
 Morris water maze test
 7-8.5 weeks
General characteristics1
 No Change
 Home cage behavior
 7-8.5 weeks
Size/growth1
 No Change
 
 7-8.5 weeks
General locomotor activity1
 No Change
 Open field test
 7-8.5 weeks
Brain morphology1
 No Change
 Histology: Histology
 7-8.5 weeks
Presynaptic function: paired-pulse facilitation1
 No Change
 
 Unreported
Synaptic plasticity1
 No Change
 
 7-8.5 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Homeostasis, Immune response, Maternal behavior, Molecular profile, Repetitive behavior, Seizure, Sensory, Social behavior

M_Grm5_2_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Brain morphology1
 No Change
 Histology: Histology
 7-8.5 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
CALM1 calmodulin 1 (phosphorylase kinase, delta) 801 P62158 GST; EMSA
Minakami R , et al. 1997
Cdk5 cyclin-dependent kinase 5 140908 Q03114 in vitro kinase assay
Orlando LR , et al. 2009
Agap2 ArfGAP with GTPase domain, ankyrin repeat and PH domain 2 216439 Q3UHD9 IP/WB
Gross C , et al. 2015
FMR1 fragile X mental retardation 1 14265 P35922 HITS-CLIP
Darnell JC , et al. 2011
GABRA1 Gamma-aminobutyric acid receptor subunit alpha-1 14394 P62812 IP/WB
Nakamura Y , et al. 2016
GABRB3 gamma-aminobutyric acid (GABA) A receptor, subunit beta 3 14402 P63080 IP/WB
Nakamura Y , et al. 2016
Gabrg2 Gamma-aminobutyric acid receptor subunit gamma-2 14406 P22723 IP/WB
Nakamura Y , et al. 2016
Gnb1 guanine nucleotide binding protein (G protein), beta 1 14688 P62874 IP/WB
Gross C , et al. 2015
Grm5 glutamate receptor, metabotropic 5 108071 Q3UVX5 IP/WB
Gross C , et al. 2015
HOMER1 homer homolog 1 (Drosophila) 26556 Q9Z2Y3 IP/WB; Bioluminescence resonance energy transfer assay
Guo W , et al. 2015
MET met proto-oncogene 17295 P16056 IP; LC-MS/MS; Proximity ligation assay; IP/WB
Xie Z , et al. 2016
Pik3cb phosphatidylinositol 3-kinase, catalytic, beta polypeptide 74769 Q8BTI9 IP/WB
Gross C , et al. 2015
Rbfox1 RNA binding protein, fox-1 homolog (C. elegans) 1 268859 Q9JJ43 HITS-CLIP
Weyn-Vanhentenryck SM , et al. 2014
Rgs17 regulator of G-protein signaling 17 56533 Q9QZB0 Bimolecular fluorescence complementation assay
Snchez-Blzquez P , et al. 2012
ADORA2A adenosine A2a receptor 135 P29274 IP/WB
Ferr S , et al. 2002
Drd2 dopamine receptor D2 13489 P61169 IP/WB; Bioluminescence resonance energy transfer assay; Bimolecular fluorescence complementation assay; Sequential resonance energy transfer (SRET)
Cabello N , et al. 2009
FLNA filamin A, alpha 281165 N/A Y2H
Enz R 2002
Frmpd4 FERM and PDZ domain containing 4 302656 D4A3K7 IP/WB
Hu JH , et al. 2012
GPRASP1 G protein-coupled receptor associated sorting protein 1 9737 Q5JY77 GST
Heydorn A , et al. 2004
Grasp GRP1 (general receptor for phosphoinositides 1)-associated scaffold protein 192254 Q8R4T5 Y2H
Kitano J , et al. 2002
Grm5 glutamate receptor, metabotropic 5 24418 P31424 IP/WB
Kitano J , et al. 2002
HOMER1 homer homolog 1 (Drosophila) 9456 Q86YM7 Y2H; IP/WB
Y2H; IP/WB; GST
Brakeman PR , et al. 1997
Homer1 homer homolog 1 (Drosophila) 29456 Q9Z214 Y2H; IP/WB
Y2H; IP/WB; GST
Brakeman PR , et al. 1997
Homer2 homer homolog 2 (Drosophila) 26557 Q9QWW1 GST
Xiao B , et al. 1998
HOMER3 homer homolog 3 (Drosophila) 9454 Q9NSC5 GST
Xiao B , et al. 1998
Ncdn neurochondrin 89791 O35095 Y2H; GST; IP/WB
Wang H , et al. 2009
Prkca protein kinase C, alpha 24680 Q9EP80 in vitro kinase assay
Kim CH , et al. 2005
Prkcb protein kinase C, beta 25023 P68403 in vitro kinase assay
Kim CH , et al. 2005
Prkcg protein kinase C, gamma 24681 P63319 in vitro kinase assay
Kim CH , et al. 2005
Prkch protein kinase C, eta 81749 Q64617 in vitro kinase assay
Kim CH , et al. 2005
Prkcq protein kinase C, theta 85420 F1LM10 in vitro kinase assay
Kim CH , et al. 2005
Prnp Prion protein 19122 P04925 IP/WB
Beraldo FH , et al. 2010
Rgs12 regulator of G-protein signaling 12 54292 O08774 Surface plasmon resonance (SPR)
Snow BE , et al. 1998
Rgs4 regulator of G-protein signaling 4 29480 P49799 IP/WB
Schwendt M and McGinty JF 2007
S100A10 S100 calcium binding protein A10 6281 P60903 in vitro binding assay; IP/WB; Co-localization
Lee KW , et al. 2015
SHANK3 SH3 and multiple ankyrin repeat domains 3 59312 Q9JLU4 GST
Tu JC , et al. 1999
Snx27 sorting nexin family member 27 260323 Q8K4V4 IP/WB
Lin TB , et al. 2015
Vps26a VPS26 retromer complex component A 361846 Q6AY86 IP/WB
Lin TB , et al. 2015

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