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.
Rescue Type:
RESCUE-Genetic
Rescue Paradigm:
Double mutant mice: null for Arhgap33 and heterozygous for Cdc42 only in post mitotic neurons ( using Nex1-Cre matings). This rescue approach was developed as Arhgap33 inactivates Cdc42 by aiding its GTPase. Neurons with lesser Cdc42 protein ( in the het ko) would therefore compensate for increased amount of active Cdc42 in the absence of Arhgap33, if Cdc42 was the main player in phenotypes seen in Arhgap33 null mice.
Treatment does not improve measured phenotype (was expected to do so)
Ameliorated
Treatment provides partial correction or improvement of measured phenotype
No adverse effect
Treatment does not affect the parameter adversely
Sustained effect
Treatment has long term effect of restoration or amelioration, tested AFTER stopping administration (not applied for continuing long-term treatment) . Will be applied only where treatment has had restorative effects during administration or in the first battery of tests conducted.
No sustained effect
Treatment has no long term of restoration or amelioration detectable, after stopping administration. Will be applied only where treatment has had restorative effects during administration or in the first battery of tests conducted.
Spontaneous post synaptic events: excitatory currents1
Refractory
Description: There is effect of loss of one copy of cdc42, in post mitotic neurons, in the frequency of spontaneous post synaptic currents in the arhgap33 mice
Exp Paradigm: NA
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 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: 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: 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
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
