Studies have found genetic association between the GRIK2 gene and autism. Positive associations have been found in the Chinese Han population among others. No association between GRIK2 and autism was found in an Indian population sample, however.
Molecular Function
Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. The subunit encoded by this gene is subject to RNA editing at multiple sites within the first and second transmembrane domains, which is thought to alter the structure and function of the receptor complex. Mutations in this gene have been associated with autosomal recessive cognitive disability.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Linkage and association of the glutamate receptor 6 gene with autism.
Mutation in a gene linked to ID in the human may lead to a transiet reduction of synaptic strength during postnatal development, impacting on the proper formation of neural circuits linked to memory.
References
Type
Title
Author, Year
Primary
Deficits in morphofunctional maturation of hippocampal mossy fiber synapses in a mouse model of intellectual disability.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Homologous recombination mediated deletion of 0.7 kb including exon coding for MD2 of Grik2 gene.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not specified
Genetic Background: C57BL6/SV129 x FVB
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
.
Allele Type: Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Grik15 knockout (5ko) mice are generated by intercrossing five mice with targeted mutations in the kainate receptor genes, which are separately located on chromosomes 16, 10, 4, 9, and 7, to produce a mouse with all five kainate receptor genes disrupted. Grik1, PMID: 11144357; Grik2, PMID: 9580260; Grik3, PMID: 17620617; Grik4, PMID: 19778510; Grik5, PMID: 12533602. Heterozygous pups (5het) from a wild-type (WT) female in the same cage were used as a control.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not specified
Genetic Background: C57BL/6:129S
ES Cell Line: 129/SvEvBrd
Mutant ES Cell Line: Not specified
Model Source: Not specified
Description: Abnormal presynaptic morphology indicated by delayed developmental profile and decreased volume of presynaptic elements
Exp Paradigm: Confocal microscopy of yfp-expression dentate gyrus granule cells
Description: Abnormal functional and morphological changes of presynaptic/postsynaptic elements indicated by marked delay in appearance of tes in ca3 pyramidal cells, smaller volume of tes
Exp Paradigm: Confocal microscopy of yfp-expression ca3 pyramidal cells
Description: Abnormal filopodia morphology indicated by decreased percentage of boutons showing filopodia, no change in number of boutons with filopodia, shorter filopodia
Exp Paradigm: NA
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission1
Abnormal
Description: Abnormal nmda/ampa components demonstrated by no change in amplitude of nmda-epsc and larget nmda/ampa ratio
Exp Paradigm: Whole-cell voltage-clamp recordings from hippocampal ca3 pyramical cells with mf-ca3 epsc's evoked by minimal intensity stimulation at low stimulation rate (0.1 hz)
Description: Abnormal low frequency mf-ca3 epsc facilitation indicated by no difference but lower extent of lff at p14-16, p19-21
Exp Paradigm: Whole-cell voltage-clamp recordings from hippocampal ca3 pyramical cells with mf-ca3 epsc's evoked by minimal intensity stimulation at low stimulation rate (0.1 hz)
Description: Abnormal quantal parameters demonstrated by no difference in p, smaller mean estimated n, and smaller q
Exp Paradigm: Multiple-probability fluctuation analysis (mpfa)
Description: Grik2 knockout mice bury significantly more marbles and spent increased fraction of time digging relative to control mice
Exp Paradigm: Marble-burying test
Description: Grik1-5 knockout (5ko) mice exhibit both increased amubulatory and increased stationary non-ambulatory movement during light-on phase, but no changes on both during light-off phase
Exp Paradigm: Home cage behavior: male mice were housed in cages for 6 days, and, after 2 days of habituation, data were collected for 4 days
Description: Grik1-5 knockout (5ko) mice exhibit decreased motor coordination and balance relative to control mice
Exp Paradigm: Accelerating rotarod test
Description: Grik1-5 knockout (5ko) mice exhibit decreased brake time and increased propel time in gait analysis relative to control mice; no changes in stride time, stride length, swing duration, and stance length
Exp Paradigm: Gait
Description: Grik1-5 knockout (5ko) mice exhibit normal length but decreased thickness of post-synaptic density in dorsal striatal neurons when comparing to the controls
Exp Paradigm: Electron microscopy
Description: Grik1-5 knockout (5ko) mice exhibit decreased spine density in both d1 and d2 spiny projection neurons when comparing to the controls
Exp Paradigm: Two-photon microscopy: analysis of spine density (secondary and tertiary dendritic segments 50200 mm from the soma)
Miniature post synaptic current frequency: excitatory1
Decreased
Description: Grik1-5 knockout (5ko) mice exhibit decreased mepsc frequency recorded in both d1 and d2 spiny projection neurons comparing to the recordings done in control mice
Exp Paradigm: Whole-cell patch clamp: voltage clamp
Description: Grik1-5 knockout (5ko) mice exhibit decreased ampa-independent epsc (resistant to gyki53655, an ampa antagonist) in spiny projection neurons (spn) comparing to the recordings done in control mice
Exp Paradigm: Whole-cell patch clamp: voltage clamp
Description: Grik1-5 knockout (5ko) mice exhibit decreased amplitude of field epsp in corticostriatal region comparing to the recordings done in control mice
Exp Paradigm: Field potential recordings
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission1
Decreased
Description: Grik1-5 knockout (5ko) mice exhibit decreased nmdar/ampar ratio in synaptic transmission of spiny projection neurons (spn) comparing to the recordings done in control mice
Exp Paradigm: Whole-cell patch clamp: voltage clamp
Description: Grik1-5 knockout (5ko) mice exhibit decreased kainic acid induced inward currents in spiny projection neurons (spn) relative to the currents recorded from control mice
Exp Paradigm: Whole-cell patch clamp: voltage clamp
Description: Grik1-5 knockout (5ko) mice bury significantly more marbles and spent increased fraction of time digging relative to control mice
Exp Paradigm: Marble-burying test
Description: Grik1-5 knockout (5ko) mice exhibit increased number of bouts and increased time spent grooming relative to control mice
Exp Paradigm: Grooming behavior assessments: the number of bouts and the time spent grooming by singly housed male mice (4-6 months old) monitored in a novel cage for a period of 30 min
Description: Grik1-5 knockout (5ko) mice exhibit no preference for the alternative arm on a successive trial in y-maze test, unlike control mice
Exp Paradigm: Y-maze test: spontaneous alternations made by mice in the y-maze are measured
