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.
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.
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:
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:
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
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
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
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
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
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
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
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
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