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.
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:
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:
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:
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:
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:
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:
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:
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:
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:
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:
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:
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:
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
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
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.
Exp Paradigm: NA
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
Exp Paradigm: NA
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
Description: A significant reduction in inhibitory synapses or contacts between putative pyramidal neurons in the hippocampal ca1 and ca3
Exp Paradigm: NA
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: Pv
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
Exp Paradigm: NA
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
Exp Paradigm: NA
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
Exp Paradigm: NA
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
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
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
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)
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
Exp Paradigm: NA
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
Exp Paradigm: NA
Description: Prepulse inhibition ratio remains significantly increased in magnitude in grm5-pvn cko compared to wild type after treatment with 2mg/kg of amphetamine
Exp Paradigm: NA
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
Exp Paradigm: NA
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
Exp Paradigm: NA
Description: Prepulse inhibition ratio remains significantly increased in magnitude in grm5-pvn cko compared to wild type after treatment with 5mg/kg of pcp
Exp Paradigm: NA
Description: Prepulse inhibition ratio remains significantly increased in magnitude in grm5-pvn cko compared to wild type after treatment with 10mg/kg of pcp
Exp Paradigm: NA
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
Exp Paradigm: NA
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
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
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
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
