Rare variants and genetic association have been found with the GRIP1 gene and autism in AGRE and SCAP cohorts (Mejias et al., 2011). In particular, that study showed convincing higher incidence of missense variants in 480 cases compared to 480 controls. Although segregation within pedigrees was not perfect, the variants were shown to be functional due to altered binding to glutamate receptor 2/3.
Molecular Function
The encoded scaffold protein mediates trafficking and membrane organization of various transmembrane proteins.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Gain-of-function glutamate receptor interacting protein 1 variants alter GluA2 recycling and surface distribution in patients with autism.
Inactivation of Grip1 causes Fraser syndrome-like defects in mice. Grip1/Grip2 double knockout mice show increased sociability in a modified three-chamber social behavioral test and in a dyadic male-male social interaction test. Immunoblot studies identified an increase in phosphorylation at GluA2-Serine 880 (GluA2-pS880) in frontal cortex and reduced GABA3 expression in striatum.
References
Type
Title
Author, Year
Primary
A direct functional link between the multi-PDZ domain protein GRIP1 and the Fraser syndrome protein Fras1.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Homologous recombination mediated targeted deletion of PDZ domain 1 of Grip1 gene.
Allele Type: Targeted (Knock Out)
Strain of Origin: C57B1/6
Genetic Background: 129 X C56B1/6
ES Cell Line: R1
Mutant ES Cell Line: Not Reported
Model Source: Not Reported
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Homologous recombination mediated targeted deletion of PDZ domain 1 of Grip1 gene.
Allele Type: Targeted (Knock Out)
Strain of Origin: C57B1/6
Genetic Background: C56B1/6
ES Cell Line: R1
Mutant ES Cell Line: Not Reported
Model Source: Not Reported
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of the first exon of the PDZ domain of the Grip1 gene using Nestin-Cre, in neuronal, glial and other cell types in the central and peripheral nervous system. The double mutant mice are generated by intercrossing the Grip1 conditonal knockout line with a Grip2 conventional knockout line.
Allele Type: Conditional loss-of-function
Strain of Origin: C57B1/6
Genetic Background: C57B1/6
ES Cell Line: Mutant ES Cell Line: Not Reported
Model Source: Not Reported
Description: Abnormal epithelial development demonstrated by detachment of oral and nasal cavities and blisters underneath head, limb, back skin
Exp Paradigm: General observations
Description: Abnormal steps of early metanephric development: no assembly of mesenchymal condensation around ureteric bud, induction of wilms' tumor antigen-1 (wt1)
Exp Paradigm: Immunofluoroscence staining of embryonic sections
Description: Abnormal developmental trajectory indicated by unstructured mesenchymal rudiments remaining devoid of metanephric tubules with large number of apoptotic cells
Exp Paradigm: Tunel & dapi staining of embryonic tissue
Description: Decreased expression of ecm proteins: collagen v, vi, substrates for ng2 and fras1 in basement membrane region
Exp Paradigm: Ecm protein expression
Description: Grip1/2 double knockout mice exhibit increased social interactions relative wildtype controls
Exp Paradigm: Reciprocal social interaction test: male only
Description: Grip1/2 double knockout mice exhibit increased sociablity and preference for social novelty relative to wildtype controls
Exp Paradigm: Three-chamber social approach test
Description: Increased level of phosphorylated glua2 at serine 880 in front cortex and cerebellum of grip1/2 double knockout mice relative to wildtype controls
Exp Paradigm: Western blot: glua2-ps880
Description: Decreased level of gababeta3 in striatum of grip1/2 double knockout mice relative to wildtype controls
Exp Paradigm: Western blot: gababeta3