Arhgef10 knockout mice were found to exhibit reduced social interaction, hyperactivity, decreased depression-like and anxiety-like behavior, increased levels of neurotransmitters including serotonin, norepinephrine, and dopamine in different brain regions, and decreased levels of monoamine oxidase A (MAO-A) in several brain regions (Lu et al., 2018). De novo and inherited missense variants in ARHGEF10 have also been identified in ASD probands (De Rubeis et al., 2014; Li et al., 2017).
Molecular Function
This gene encodes a Rho guanine nucleotide exchange factor (GEF). Rho GEFs regulate the activity of small Rho GTPases by stimulating the exchange of guanine diphosphate (GDP) for guanine triphosphate (GTP) and may play a role in neural morphogenesis. Mutations in this gene are associated with slowed nerve conduction velocity (SNCV).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Impairment of social behaviors in Arhgef10 knockout mice.
Arhgef10 knockout mice showed social interaction impairment, hyperactivity, and decreased depression-like and anxiety-like behavior and no change in spatial learning in the Morris water maze. Neurotransmitters serotonin, norepinephrine, and dopamine were increased in different brain regions of the Arhgef10 knockout mice. Monoamine oxidase A (MAO-A) levels were decreased in several brain regions of the Arhgef10 knockout mice (Lu D-H, Mol. Aut., 2018).
References
Type
Title
Author, Year
Primary
Impairment of social behaviors in Arhgef10 knockout mice.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Arhgef10 knockout mice were generated by the deletion of exon 4 and exon 5 using the Cre-loxP site-specific knockout. .
Allele Type: Knockout
Strain of Origin: 129S1/Sv
Genetic Background: C57BL/6J
ES Cell Line: 129S1/Sv
Mutant ES Cell Line: 129S1/Sv
Model Source: 29456827
Description: Mutants show decrease in mao-a levels in the frontal cortex and amygdala in comparison with controls.
Exp Paradigm: Mao-a and mao-b are the key enzymes that degrade ne and 5-ht.
Description: Mutants show increased serotonin content in the frontal cortex and amygdala in comparison with wildtype controls.
Exp Paradigm: The frontal cortex, striatum, hippocampus, and amygdala were analyzed by hplc with electrochemical detection (ecd) to determine the content of dopamine, 5-ht, ne, and their metabolites.
Description: Mutants show increased norepinephrine in the frontal cortex and amygdala in comparison with wildtype controls.
Exp Paradigm: The frontal cortex, striatum, hippocampus, and amygdala were analyzed by hplc with electrochemical detection (ecd) to determine the content of dopamine, 5-ht, ne, and their metabolites.
Description: Mutants show increased dopamine content in the striatum and amygdala in comparison with wildtype controls.
Exp Paradigm: The frontal cortex, striatum, hippocampus, and amygdala were analyzed by hplc with electrochemical detection (ecd) to determine the content of dopamine, 5-ht, ne, and their metabolites.
Description: Mutants spend less time in the chamber containing the second unfamiliar mouse compared to controls. mutants show no change in time spent interacting with the first or second unfamiliar mouse compared to controls.
Exp Paradigm: C57bl/6j mice were used as the stranger mice.
Description: Mutants spend more time in the open arms of the elevated plus maze compared to controls. mutants showed increased number of entries into the open arms of the elevated plus maze compared to controls.
Exp Paradigm: NA
Description: Mutants show decreased expression of arhgef10 in the whole brain compared to controls. mutants show no expression of arhgef10 in the brain whereas wildtype controls show arhgef10 protein expressed in the frontal cortex, striatum, hippocampus, and amygdala.
Exp Paradigm: NA
