Mice with Sh3rf2 haploinsufficiency exhibited significant deficits in social interactionand communication, stereotyped and repetitive behaviors, hyperactivity, and seizures, as well as unilateral disturbances in hippocampal dendritic spine development, aberrant composition of glutamatergic receptor subunits, and abnormal excitatory synaptictransmission (Wang et al., 2018).
Molecular Function
The protein encoded by this gene has E3 ubiquitin-protein ligase activity, acts as an anti-apoptotic regulator of the JNK pathway by ubiquitinating and promoting the degradation of SH3RF1, a scaffold protein that is required for pro-apoptotic JNK activation, and facilitates TNF-alpha-mediated recruitment of adapter proteins TRADD and RIPK1 to TNFRSF1A and regulates PAK4 protein stability via inhibition of its ubiquitin-mediated proteasomal degradation.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Sh3rf2 Haploinsufficiency Leads to Unilateral Neuronal Development Deficits and Autistic-Like Behaviors in Mice.
Sh3rf2 het mutant mice show deficits in social interaction, and communication, increase in repetetive behavior, hyperactivity, seizures, and unilateral left-hemisphere specific defects in development of dendritic spines in the hippocampus, composition of glutamatergic receptor subunits, and excitatory synaptic transmission.
References
Type
Title
Author, Year
Primary
Sh3rf2 Haploinsufficiency Leads to Unilateral Neuronal Development Deficits and Autistic-Like Behaviors in Mice.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Sh3rf2 homozygous knockout mice were generated by replacing 138 bps of exon1 which code for the first 126 residues with nLacZ-SV40-polyA and the neomycin resistance gene. To obtain GFP labeled neurons, Thy1-GFP line-M transgenic mice in a C57BL6 background were interbred with Sh3rf2 mutant mice.
Allele Type: Knockout
Strain of Origin: Not specified
Genetic Background: C57/BL6N
ES Cell Line: C57BL/6-derived ES cells
Mutant ES Cell Line: Model Source: Beijing Vital River Laboratory Animal Technology
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Sh3rf2 heterozygous knockout mice were generated by replacing 138 bps of exon1 which code for the first 126 residues with nLacZ-SV40-polyA and the neomycin resistance gene. To obtain GFP labeled neurons, Thy1-GFP line-M transgenic mice in a C57BL6 background were interbred with Sh3rf2 mutant mice.
Allele Type: Knockout
Strain of Origin: Not specified
Genetic Background: C57/BL6N
ES Cell Line: C57BL/6-derived ES cells
Mutant ES Cell Line: Model Source: Beijing Vital River Laboratory Animal Technology
Description: Mutants show decrease in birth rates in both males and females compared with controls. male homozygous mutants show increased mortality during postnatal development compared with controls.
Exp Paradigm: NA
Genotypic ratio of progeny from heterozygous parents
Description: Mutants show increase in glur2 in the right but not left hippocampus compared with controls indicating lateralization of the phenotype. mutants show no significant changes in glur1 levels in the hippocampus bilaterally compared with controls.
Exp Paradigm: NA
Description: Mutants show decreased volumes of mushroom, stubby, and filopodia spines in secondary basal dendrites of the left but not the right hippocampal ca1 pyramidal neurons compared with controls, indicating a defect in brain lateralization. mutants show decreased volumes of mushroom, stubby, and filopodia spines in apical dendrites of the left but not the right hippocampal ca1 pyramidal neurons compared with controls. mutants show decreased volumes of filopodia spines in the apical dendrites of the right hippocampal ca1 pyramidal neurons compared with controls.
Exp Paradigm: Ca1 pyramidal neurons were labelled with thy1-gfpm.
Description: Mutants show increase in nr2a left but not right hippocampus compared with controls indicating lateralization of the phenotype. mutants show no significant changes in nr2b levels in the hippocampus bilaterally compared with controls.
Exp Paradigm: NA
Miniature post synaptic current frequency: excitatory1
Abnormal
Description: Mutants show an decrease in the frequency of mepscs in pyramidal neurons of the left ca1 region but a increase in the right, compared with controls, indicating a defect in brain lateralization.
Exp Paradigm: NA
Description: Mutants show a decrease in the after hyperpolarization potential (ahp), and membrane capacitance in the right hippocampus but not in the left hippocampus, compared with controls. mutants show an increase in membrane resistance in the right ca1 region of the hippocampus but not the left compared with controls. these indication lateralization of the phenotype.
Exp Paradigm: NA
Description: Mutants show increase in spike frequency in the pyramidal neurons of the left hippocampal ca1 region but not the right compared with respective wildtype controls, indicating a defect in brain lateralization.
Exp Paradigm: NA
Description: Mutants spent less time interacting with an unfamiliar mouse compared with controls.
Exp Paradigm: Both test and control pups were nurtured by sh3rf2 mothers.
Description: Mutants show decrease in time spent in social behaviors in free dyadic social interaction compared with controls.
Exp Paradigm: Both test and control pups were nurtured by sh3rf2 mothers.
Description: Mutants show reduction in time spent in close interaction with an unfamiliar mouse compared with controls.
Exp Paradigm: Both test and control pups were nurtured by sh3rf2 mothers.
Description: Mutant pups show decrease in duration of ultrasonic vocalization calls when isolated from their mothers compared with controls, although the number of calls, the latency to start calling or the peak call frequency were not altered.
Exp Paradigm: Both test and control pups were nurtured by sh3rf2 mothers.
Ultrasonic vocalization: interaction induced: opposite sex stimulus1
Decreased
Description: Mutants show decrease in the usv call duration although the number of calls, the latency to start calling or the peak call frequency were not altered.
Exp Paradigm: Both test and control pups were nurtured by sh3rf2 mothers.
