Maternally-inherited frameshift (A94fs199X) and missense (Y236S and G464R) variants in SYN2 were found to be associated with ASD in male cases (Corradi et al., 2013). Deletion of SYN2 in mice extensively impaired various aspects of social behavior and memory, altered exploration of a novel environment and increased self-grooming (Greco et al., 2013).
Molecular Function
This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. This member of the synapsin family encodes a neuron-specific phosphoprotein that selectively binds to small synaptic vesicles in the presynaptic nerve terminal. Mutations in this gene may be associated with abnormal presynaptic function and schizophrenia.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
SYN2 is an autism predisposing gene: loss-of-function mutations alter synaptic vesicle cycling and axon outgrowth.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Synapsin II knockout.
Allele Type: Strain of Origin: Genetic Background: C57BL/6J
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: Greengard laboratory (PMID 9513186)
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Synapsin II knockout.
Allele Type: Strain of Origin: Genetic Background: C57BL/6J
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: Greengard laboratory (PMID 9513186)
Description: Synii ko pups spent more time to right their body than wt and het pups.
Exp Paradigm: Frequency and duration of behavioral patterns showed by synii pups during 3 min of maternal separation was measured.
Functional magnetic resonance imaging: connectivity2
Decreased
Description: Synii ko male mice showed no change in global connectivity strength compared to controls. synii ko male mice showed bilateral foci of decreased local connectivity in auditory and somatosensory cortices and intermediate hippocampus in local (short range, <0.6 mm) connectivity mapping compared to wt littermates. local connectivity in auditory areas and intermediate hippocampus correlated with usv calls impairment in individual subjects. synii ko male mice showed reduced inter-hemispheric connectivity between the auditory cortex and its homotopic contralateral regions compared to controls. synii ko male mice showed no change in inter-hemispheric connectivity between homologous brain regions in the insular cortex, primary motor cortex, somatosensory cortex, and
Exp Paradigm: To identify macroscale functional substrates involved in the behavioral alterations local and long-range connectivity was mapped using rsfmri. mice were under shallow halothane anesthesia.
Functional magnetic resonance imaging (fmri)-resting state
Description: Decreased social recognition indicated by failure to increased exploration of novel vs. intruder mouse
Exp Paradigm: Social recognition test
Description: Synii ko male mice spent less time investigating a c57bl/6j female partner than wt mice. synii ko male mice approached a receptice c57bl/6j female partner with less frequency than wt mice.
Exp Paradigm: Total sniffing time was measured.
Description: Decreased aggression indicated by reduced social interaction with intruder after 1-2 months of social isolation
Exp Paradigm: Resident intruder test
Description: Decreased social novelty indicated by failure to discirminate between familiar vs. novel mouse
Exp Paradigm: Social novelty phase of three-chambered social approach test
Description: Synapsin ii homozygous knockout pups separated from their mothers show decrease in the number of calls per minute, in the total duration of the calls, but no change in the categories of calls emitted, compared to controls.
Exp Paradigm: 3-min maternal separation test. peak frequency, amplitude and total duration of the call were measured. call categories were analyzed: cx=complex, tc=two-component, up=upward, dw=downward, ch=chevron, sh=short, cp=composite, fs=frequency steps, fl=flat, un=unstructured.
Ultrasonic vocalization: interaction induced: opposite sex stimulus2
Decreased
Description: Adult synapsin ii homozygous male mice show changes in various categories (cx, tc, up, dw, fs) of calls emited during courtship compared to controls. adult synapsin ii homozygous male mice show reduction in the duration of calls during courtship compared to controls.
Exp Paradigm: 3-min maternal separation test. peak frequency, amplitude and total duration of the call were measured. call categories were analyzed: cx=complex, tc=two-component, up=upward, dw=downward, ch=chevron, sh=short, cp=composite, fs=frequency steps, fl=flat, un=unstructured.
