Rare mutations in the SHANK1 gene have been identified in individuals with ASD (Sato et al., 2012).
Molecular Function
Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and Homer, respectively, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
SHANK1 Deletions in Males with Autism Spectrum Disorder.
A recurrent SHANK1 mutation implicated in autism spectrum disorder causes autistic-like core behaviors in mice via downregulation of mGluR1-IP3R1-calcium signaling
A recurrent SHANK1 mutation implicated in autism spectrum disorder causes autistic-like core behaviors in mice via downregulation of mGluR1-IP3R1-calcium signaling
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Targeted replacement of exons 14 and 15 encoding the entire PDZ domain was replace with the PGK-neo cassette.
Allele Type: Targeted (Knock Out)
Strain of Origin: C57BL/6
Genetic Background: C57BL/6J/129SvJae (B6/Jae)
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Targeted replacement of exons 14 and 15 encoding the entire PDZ domain was replace with the PGK-neo cassette.
Allele Type: Targeted (Knock Out)
Strain of Origin: C57BL/6
Genetic Background: C57BL/6J/129SvJae (B6/Jae)
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Shank1 sequence was manipulated via knockin R882H substitution, corresponding to a human R874H substitution.
Allele Type: ASD mutation
Strain of Origin: Genetic Background: C57BL/6N
ES Cell Line: Mutant ES Cell Line: Model Source: Hongyan Wang Lab (PMID 35388181)
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Shank1 sequence was manipulated via knockin R882H substitution, corresponding to a human R874H substitution.
Allele Type: ASD mutation
Strain of Origin: Genetic Background: C57BL/6N
ES Cell Line: Mutant ES Cell Line: Model Source: Hongyan Wang Lab (PMID 35388181)
Description: Decreased righting response indicated by longer time to flip over onto abdomen with four paws touching the surface
Exp Paradigm: Measure of time taken by animal to correct itself after being placed on it's back
Description: Decreased locomotor activity indicated by lower distance traveled and lower number of rearing in clean environment
Exp Paradigm: Male mice: open field test in clean environment
Description: Decreased locomotor activity indicated by lower distance traveled and lower number of rearing after female experience with female urine
Exp Paradigm: Male mice: open field test with female experience through female urine
Description: Abnormal synapse morphology indicated by decreased mean spine density and smaller spine size
Exp Paradigm: Quantitative analysis of apical dendritic spines of ca1 pyramidal neurons of hippocampus
Description: Decreased synapse ultrastructure indicated by reduced thickness and length of psd in hippocampal ca1 region
Exp Paradigm: Thin-section electron microscopic micrographs from brains
Description: Decreased basal synaptic transmission indicated by significantly downward shifted input-output curve at high stimulus intensities
Exp Paradigm: Extracellular recordings of ampa receptor-mediated field epsps in the striatum radiatum
Description: Abnormal ampar mediated mepsc shown by no difference in average mepsc amplitude and decreased frequency of mepsc
Exp Paradigm: Whole-cell patch clamping of brain slices
Description: Decreased scent marking indicated by fewer urine traces in proximity to female urine spot and also less time spent in proximity to urine spot
Exp Paradigm: Male mice: scent marking behavior in presence of female urine
Description: Abnormal ultrasonic vocalizations indicated by no increase in number of calls across isolation, no increase in time spent vocalizing, no increase in call duration, no increase in call frequency modulation
Exp Paradigm: Female mice: ultrasonic vocalizations in maternally isolated pups test
Description: Abnormal ultrasonic vocalization calling pattern indicated by failure to change after prior female experience
Exp Paradigm: Male mice: ultrasonic vocalization calling pattern in response to presence of female urine
Description: Decreased ultrasonic vocalizations demonstrated by fewer usv's emitted, reduced calling time, reduced call repitition rate, affected peak frequency of calls, less frequency modulated usvs
Exp Paradigm: Female mice: ultrasonic vocalizations in maternally isolated pups test
Description: Increased anxiety demonstrated by fewer transitions between compartments and longerl atency to enter light side
Exp Paradigm: Light/dark test
Description: Decreased long term memory indicated by regression of reference memory performance
Exp Paradigm: Long-term stability of eight-arm radial maze task
Description: Abnormal expression of glutamate receptors, scaffold proteins, and signaling molecules with reduction of gkap, homer1b/c
Exp Paradigm: Protein expression pattern
Description: Differences in gray matter volume were obtained in the frontal cortex (including septal area), striatum, piriform area, thalamus, hippocampus and cerebellar cortex.
Description: Differences in gray matter volume were obtained in the frontal cortex (including septal area), striatum, piriform area, thalamus, hippocampus and cerebellar cortex.
Description: Homozygous KI mice show disturbed glutamate-induced calcium signaling measured by decrease fluorescence in response to DHPG and glutamate.
Description: Differences in gray matter volume were obtained in the frontal cortex (including septal area), striatum, piriform area, thalamus, hippocampus and cerebellar cortex.
Description: Postsynaptic density of glutamatergic synapses in hippocampal CA1 neurons length was increased by 17% in KI homozygous mice. A reduction of 10% was observed in the thickness of the PSDs.
Description: Differences in gray matter volume were obtained in the frontal cortex (including septal area), striatum, piriform area, thalamus, hippocampus and cerebellar cortex.
Description: Differences in gray matter volume were obtained in the frontal cortex (including septal area), striatum, piriform area, thalamus, hippocampus and cerebellar cortex.
Description: Differences in gray matter volume were obtained in the frontal cortex (including septal area), striatum, piriform area, thalamus, hippocampus and cerebellar cortex.
Description: Recordings at SCCA1 synapses show that long-term potential (LTP) induced by theta burst stimulation (TBS) of the SCs is severely impaired in homozygous KI mice from the induction period to the maintenance period.
Description: In RNA-Seq analysis of mRNAs in the hippocampus in Shank1 R882H-KI homozygous and WT mice, 23718 genes were identified only 14 genes showed significant changes.
Description: Homozygous KI mice show reductions in phosphorylated ERK1/2: 24.6% in the frontal cortex, 35.4% in the hippocampus and 37.0% in the cerebellar cortex.
Description: Levels of Homer family proteins were significantly reduced in three brain regions of homozygous R882H-KI mice: decrease of 25% was observed for Homer1 in the hippocampus, a decrease of 30.6% was observed for Homer2 in the frontal cortex, and a decrease of 34.4% was observed for Homer3 in the cerebellar cortex.
