SHANK3
Encyclopedia
SH3 and multiple ankyrin repeat domains 3, also known as SHANK3, is a human gene
on chromosome 22.
This gene is a member of the Shank gene family. Shank proteins are multidomain scaffold proteins of the postsynaptic density that connect neurotransmitter
receptors, ion channels, and other membrane proteins to the actin cytoskeleton and G-protein-coupled signaling pathways. Shank proteins also play a role in synapse formation and dendritic spine maturation. Mutations in this gene are a cause of autism spectrum disorder (ASD) which is characterized by impairments in social interaction and communication, and restricted behavioral patterns and interests. Mutations in this gene are a major causitive factor in the neurological symptoms of 22q13.3 deletion syndrome. Additional isoforms have been described for this gene but they have not yet been experimentally verified. [provided by RefSeq]
type glutamate receptors subunit NR1. PMID 21565394 The heterozygous mutant mice display autism-like behavioral deficits and also exhibit schizophrenia-like phenotypes, consistent with altered glutamate receptor function. Consistent with this, the mice have deficits in NMDA LTP
, LTD
and enhanced mGluR LTD similar to Fragile-X. These results suggest that NMDA receptor degradation could be a shared feature of both Autism and Schizophrenia.
Other mouse models of Shank3 include N-terminal knock-outs PMID 21558424 and PMID 21167025 and a PDZ domain knock-out PMID 21423165 all of which also show social interaction deficits and variable other phenotypes. Most of the these mice are homozygous knock-outs whereas all the human Shank3 mutations have been heterozygous.
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
on chromosome 22.
This gene is a member of the Shank gene family. Shank proteins are multidomain scaffold proteins of the postsynaptic density that connect neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
receptors, ion channels, and other membrane proteins to the actin cytoskeleton and G-protein-coupled signaling pathways. Shank proteins also play a role in synapse formation and dendritic spine maturation. Mutations in this gene are a cause of autism spectrum disorder (ASD) which is characterized by impairments in social interaction and communication, and restricted behavioral patterns and interests. Mutations in this gene are a major causitive factor in the neurological symptoms of 22q13.3 deletion syndrome. Additional isoforms have been described for this gene but they have not yet been experimentally verified. [provided by RefSeq]
Mouse Models
Bangash et al. created a gain-of-function transgenic mouse bearing a deletion at the C terminus of Shank3 that mimics clinical mutations and define a biochemical pathway linking mutant Shank3 to the proteasomal degradation of Shank3 and NMDANMDA
N-Methyl-D-aspartic acid or N-Methyl-D-aspartate is an amino acid derivative which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor...
type glutamate receptors subunit NR1. PMID 21565394 The heterozygous mutant mice display autism-like behavioral deficits and also exhibit schizophrenia-like phenotypes, consistent with altered glutamate receptor function. Consistent with this, the mice have deficits in NMDA LTP
LTP
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, LTD
LTD
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and enhanced mGluR LTD similar to Fragile-X. These results suggest that NMDA receptor degradation could be a shared feature of both Autism and Schizophrenia.
Other mouse models of Shank3 include N-terminal knock-outs PMID 21558424 and PMID 21167025 and a PDZ domain knock-out PMID 21423165 all of which also show social interaction deficits and variable other phenotypes. Most of the these mice are homozygous knock-outs whereas all the human Shank3 mutations have been heterozygous.