Recombinant Mouse SH3 and multiple ankyrin repeat domains protein 3 (Shank3), partial

1. The study supports a dissociation of Shank3 functions in cortical and striatal neurons in autism spectrum disease-related behaviors, and it illustrates the complexity of neural circuit mechanisms underlying these behaviors. PMID: 29700290
2. Describe a complete knockout mouse model of the autism-associated Shank3 gene, with a deletion of exons 4-22 (Deltae4-22). Both mGluR5-Homer scaffolds and mGluR5-mediated signalling are selectively altered in striatal neurons. These changes are associated with perturbed function at striatal synapses, abnormal brain morphology, aberrant structural connectivity and autism spectrum disorder-like behaviour. PMID: 27161151
3. The Shank3/F model, and to a much lesser extent, the Shank3/J and Cacna1c models, showed hypoactivity and a general anxiety-like behavior triggered by external stimuli which pervaded social interactions. PMID: 28753255
4. Mutations/deletions in the SHANK3 gene are associated with autism spectrum disorders and intellectual disability. PMID: 27492494
5. Results suggest age-dependent decrease of GAD65/67 mRNAs but normal densities of certain GABAergic interneurons in the Shank3 transgenic mice. PMID: 28400125
6. In a Shank3 Deltaex(4-9) mouse model the excitatory synaptic transmission within the ventral tegmental area is not affected. PMID: 28002633
7. Together, our results showing that zinc affected the Shank3 protein interactions of in vitro mouse synaptosomes provided an additional link between zinc and core synaptic proteins that have been implicated in multiple brain disorders. PMID: 29111324
8. Results show that pairwise discrimination associative learning is disrupted in +/- Shank3B mice (heterozygous for exon 13-16, coding for the PDZ domain, deletion), opening a new pathway to study neurobiological mechanisms behind intellectual disabilities caused by deletions/mutations in SHANK3. PMID: 27189882
9. Shank3 deletion preferentially affects synapses onto striatopallidal MSNs. Striatopallidal MSNs showed profound defects, including alterations in synaptic transmission, synaptic plasticity, and spine density. PMID: 28414301
10. a mouse model of autism with deletions in Shank3 (Shank3B-/-) shows early cortical hyperactivity, which triggers increased SPN excitatory synapse and corticostriatal hyperconnectivity. PMID: 26928064
11. used shRNA to model Shank3 insufficiency in the ventral tegmental area of mice PMID: 27273769
12. Homozygous and heterozygous Shank3 complete knockout (Deltae4-22) results in impaired heat hyperalgesia in inflammatory and neuropathic pain. SHANK3 interacts with transient receptor potential subtype V1 (TRPV1) via Proline-rich region and regulates TRPV1 surface expression. PMID: 27916453
13. we characterized the behavioral, molecular and electrophysiological phenotypes of Shank3 mutant mice that were generated by deleting exon 11. The results of our molecular studies further indicate that Shank3 plays a major role in modulating mGlu5 signaling by regulating Homer recruitment/localization to the PSD in brain regions that are highly associated with ASD-like behavior. PMID: 27021819
14. SHANK1 and SHANK3 act as integrin activation inhibitors by sequestering active Rap1 and R-Ras via the SPN domain and thus limiting their bioavailability at the plasma membrane. PMID: 28263956
15. In the hippocampus, changes in synaptic Shank3 levels are influenced by circadian rhythm/melatonin concentration, while running activity increases and decreases levels of Shank3 in the cortex and striatum respectively PMID: 27329942
16. Shank3 is a multi-domain, synaptic scaffolding protein that organizes proteins in the postsynaptic density of excitatory synapses. PMID: 26559786
17. Cortical neurons cultured on MEAs displayed a rich repertoire of spontaneous firing, and Shank3 deletion led to reduced firing. MEA recordings revealed electric phenotypes that displayed altered excitation and inhibition in the network lacking Shank3. PMID: 26598066
18. reduction of PV(+) neurons was in all cases, i.e., in PV+/-, Shank1-/- and Shank3B-/- mice, was due to a reduction in Pvalb mRNA and PV protein. PMID: 26819149
19. post-transcriptional regulation of SHANK3 expression by three microRNAs (miRNAs), miR-7, miR-34a, and miR-504, is reported. PMID: 26572867
20. differential Shank3 mRNA stability and SHANK1/2 upregulation in mutant mice with Shank3 mutations linked to autism spectrum disorder and schizophrenia PMID: 26687841
21. social deficits and NMDAR hypofunction are rescued by inhibiting cofilin or activating Rac1 in Shank3-deficient mice PMID: 26027926
22. results reveal the profound effect of post-developmental activation of Shank3 expression on neural function, and demonstrate a certain degree of continued plasticity in the adult diseased brain PMID: 26886798
23. Since mutations in all three human SHANK genes are linked to neuropsychiatric disorders such as autism and schizophrenia, Shank mutant mice serve as corresponding in vivo model systems--{REVIEW} PMID: 25917711
24. This study demonstrated that Autism-Associated Insertion Mutation (InsG) of Shank3 Exon 21 Causes Impaired Synaptic Transmission and Behavioral Deficits in mice. PMID: 26134648
25. results indicate that behavioral phenotypes associated with Shank3 haploinsufficiency are largely strain-independent PMID: 24652766
26. prenatal zinc deficiency as a risk factor for autism spectrum disorder may unfold through the deregulation of zinc-binding ProSAP/Shank family members PMID: 24277719
27. identified two novel splicing Shank3 transcript variants whose transcriptional initiation sites are located in intron 10 PMID: 24164323
28. These data suggest that Shank3 isoforms are required for normal synaptic transmission/plasticity in the hippocampus, as well as hippocampus-dependent spatial learning and memory. PMID: 24259569
29. Shank3 directly interacts with the Arp2/3 complex to increase F-actin levels in Shank3 transgenic mice PMID: 24153177
30. Shank3-Rich2 interaction is increased in dendritic spines of hippocampal neurons during long-term potentiation. PMID: 23739967
31. Shank3 null mutant mice show reduced glutamatergic transmission and long-term potentiation in the hippocampus with more severe deficits detected in homozygous compared to heterozygous mice. PMID: 22573675
32. Data conclude that loss of major Shank3 species produces biochemical, cellular and morphological changes, leading to behavioral abnormalities in mice that bear similarities to human ASD patients with SHANK3 mutations. PMID: 21558424
33. Shank3 protein has a role in regulating metabotropic glutamate receptor 5 (mGluR5) expression and signaling at synapses PMID: 21795692
34. findings demonstrate a critical role for SHANK3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic-like behaviours in mice PMID: 21423165
35. Scaffolding proteins ProSAP1/2 were found within the postsynaptic specializations of synapses within the PNS, indicating a similar molecular assembly of central and peripheral postsynapses. PMID: 20800661
36. These results demonstrate that the Shank3 adaptor protein can mediate cellular signaling, and provide a molecular mechanism for the biological divergence between the Ret9 and Ret51 isoform. PMID: 15569713
37. Shank promotes the assembly of a signaling complex at corticostriatal synapses that enables key GPCRs to regulate L-type Ca2+ channels and the integration of glutamatergic synaptic events. PMID: 15689540
38. These results strongly suggest that Shank 3 proteins and the associated glutamate receptors participate in a concerted manner to form spines and functional synapses. PMID: 15814786
39. Taken together with the biochemical interaction of Shank3 with the GluR1 subunit, these results suggest that Shank3 is an important molecule that interacts with GluR1 AMPA receptor at synaptic sites of developing neurons. PMID: 16606358

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KEGG: mmu:58234

STRING: 10090.ENSMUSP00000048062

UniGene: Mm.146855