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Relevance to Autism

A mouse model with a loss-of-function mutation in the ARHGAP33 gene exhibited altered social behavior and dendritic spine and synapse development (Schuster et al., 2015).

Molecular Function

This gene encodes a member of the sorting nexin family. Members of this family are involved in intracellular trafficking.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
NOMA-GAP/ARHGAP33 regulates synapse development and autistic-like behavior in the mouse.
Support
Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
ASD
Support
Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.
DD, epilepsy/seizures
Support
Integrating de novo and inherited variants in 42
ASD

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN713R001a 
 missense_variant 
 c.1495G>A 
 p.Val499Met 
 Familial 
 Both parents 
 Multiplex 
 GEN713R002 
 frameshift_variant 
 c.3166_3167del 
 p.His1056Ter 
 Familial 
 Paternal 
 Multiplex 
 GEN713R003 
 splice_site_variant 
 c.93+1dup 
  
 De novo 
  
  
 GEN713R004 
 missense_variant 
 c.1084C>T 
 p.Arg362Trp 
 De novo 
  
  
 GEN713R005 
 synonymous_variant 
 c.1779G>C 
 p.Thr593%3D 
 De novo 
  
  
 GEN713R006 
 missense_variant 
 c.2207G>A 
 p.Arg736Gln 
 De novo 
  
  
 GEN713R007 
 missense_variant 
 c.2207G>A 
 p.Arg736Gln 
 De novo 
  
 Simplex 

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model

Model Summary

Arhgap33 knock out mice have normal sensory function, including vision and olfaction. They show reduced social behavior and increased dendritic spine density in the neocortex.

References

Type
Title
Author, Year
Primary
NOMA-GAP/ARHGAP33 regulates synapse development and autistic-like behavior in the mouse.

M_ARHGAP33_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Exons 7 - 12 were replaced with a lacZ gene with a nuclear localization signal and a self-excising neo cassette via homologous recombination in embryonic stem cells.
Allele Type: Targeted(Knockout)
Strain of Origin:
Genetic Background: C57Bl/6
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_ARHGAP33_1_KO_HM_EGFP

Model Type: Genetic
Model Genotype: Homozygous
Mutation: In utero electroporation iof enhanced-GFP in the developing cortex of embryos at E15.5 was carried out, Arhgap33 homozygous knockout mice with the eGFP were analyzed.
Allele Type: Targeted(Knockout)
Strain of Origin:
Genetic Background: C57Bl/6
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_ARHGAP33_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Clasping reflex1
Increased
Description: There is increased hindlimb clasping in male arhgap33 null mice compared to male controls
Exp Paradigm: Males
 Tail suspension test
 Adult
Spontaneous post synaptic events: excitatory currents1
Decreased
Description: There is significantly reduced frequency of spontaneous post synaptic currents in the upper layer cortical neurons in brain slices from arhgap33 null mice
Exp Paradigm: NA
 Whole-cell patch clamp
 Adult
Social memory1
Decreased
Description: Male arhgap33 null mice show signficantly reduced social memory compared to control males, three-chamber social approach test, displaying no preference to an unfamiliar mouse over a familiar mouse
Exp Paradigm: Males
 Three-chamber social approach test
 Adult
Social approach1
Decreased
Description: Male arhgap33 null mice show signficantly reduced social approach or sociability compared to control males, in both the partition test and three-chamber social approach test, towards an unfamiliar mouse.
Exp Paradigm: Males-partition test
 Partition test
 Adult
Social approach1
Decreased
Description: Male arhgap33 null mice show signficantly reduced social approach or sociability compared to control males, in both the partition test and three-chamber social approach test, towards an unfamiliar mouse.
Exp Paradigm: Males- three-chamber social approach test
 Three-chamber social approach test
 Adult
Nest building behavior1
Increased
Description: Both male and female arhgap33 null mice show significantly increased nest building behavior, building complex nests, which may be an indication of anxiety as well, the authors have noted
Exp Paradigm: NA
 Nest building assay
 Adult
Anxiety1
Increased
Description: There is a significant trend in increased anxiety seen in both male and female arhgap33 null mice over a variety of tests, including marble-burying and open field test. even if there is some differences in the types of test the sexes show increased anxiety in, in several parameters both male and female mice show increased anxiety.
Exp Paradigm: Female mice show some differences in the types of tests for anxiety. they show increased grooming and increased latency to enter the center in the open field (novel env.). both male and female mice show increased burrowing and decreased latency to bury marbles showing an increase in anxiety levels, while males also show increased freezing bouts in the open field (novel env.)- open field test: freezing, grooming
 Open field test
 Adult
Anxiety1
Increased
Description: There is a significant trend in increased anxiety seen in both male and female arhgap33 null mice over a variety of tests, including marble-burying and open field test. even if there is some differences in the types of test the sexes show increased anxiety in, in several parameters both male and female mice show increased anxiety.
Exp Paradigm: Female mice show some differences in the types of tests for anxiety. they show increased grooming and increased latency to enter the center in the open field (novel env.). both male and female mice show increased burrowing and decreased latency to bury marbles showing an increase in anxiety levels, while males also show increased freezing bouts in the open field (novel env.)- defensive burying test
 Defensive burying test
 Adult
Anxiety1
Increased
Description: There is a significant trend in increased anxiety seen in both male and female arhgap33 null mice over a variety of tests, including marble-burying and open field test. even if there is some differences in the types of test the sexes show increased anxiety in, in several parameters both male and female mice show increased anxiety.
Exp Paradigm: Female mice show some differences in the types of tests for anxiety. they show increased grooming and increased latency to enter the center in the open field (novel env.). both male and female mice show increased burrowing and decreased latency to bury marbles showing an increase in anxiety levels, while males also show increased freezing bouts in the open field (novel env.)-marble-burying test
 Marble-burying test
 Adult
Locomotor activity in diurnal cycle1
 No change
 Home cage behavior
 Adult
Coat color1
 No change
 NA
 NA
Skeletal development1
 No change
 NA
 NA
Exploratory activity1
 No change
 Open field test
 Adult
Clasping reflex1
 No change
 Tail suspension test
 NA
Gait1
 No change
 NA
 Adult
General locomotor activity1
 No change
 NA
 Adult
Grip strength1
 No change
 Grip strength test
 Adult
Motor strength and endurance1
 No change
 NA
 NA
Righting response1
 No change
 NA
 Adult
Self grooming: home cage/familiar environment1
 No change
 NA
 NA
Spontaneous and reflexive eye movements1
 No change
 Corneal reflex test
 NA
Tremor1
 No change
 NA
 Adult
Walking backwards1
 No change
 NA
 Adult
Spontaneous post synaptic event amplitude: excitatory currents1
 No change
 Whole-cell patch clamp
 Adult
Respiratory function1
 No change
 NA
 Adult
Stereotypy1
 No change
 NA
 Adult
Olfaction1
 No change
 Buried food test
 Adult
Startle response: acoustic stimulus1
 No change
 Acoustic startle reflex test
 Adult
Vision1
 No change
 Cliff avoidance test
 Adult
Social approach1
 No change
 Partition test
 Adult
 Not Reported: Communications, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Physiological parameters, Seizure

M_ARHGAP33_1_KO_HM_EGFP

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Dendritic architecture: spine density1
Increased
Description: There is increased spine density in the upper cortical layers(2/3) of arhgap33 null mice, visualized by egfp.
Exp Paradigm: NA
 Fluorescence microscopy
 3 weeks
Dendritic architecture: dendritic tree complexity1
Increased
Description: There is an increase in spine neck length, in average, in layer 2/3 of the cortex. increased spine length may be indicative of immature spines according to the authors
Exp Paradigm: NA
 Fluorescence microscopy
 3 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
NTRK2 neurotrophic receptor tyrosine kinase 2 4915 Q16620 IP/WB; Co-localization
Nakazawa T , et al. 2016
SORT1 sortilin 1 6272 Q99523 IP/WB; Co-localization
Nakazawa T , et al. 2016
Dlg2 discs, large homolog 2 (Drosophila) 23859 Q91XM9 IP/WB
Schuster S , et al. 2015
Dlg3 discs, large homolog 3 (Drosophila) 53310 P70175 IP/WB
Schuster S , et al. 2015
Dlg4 Postsynaptic density protein 95 13385 Q62108 IP/WB; Co-localization
Schuster S , et al. 2015

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