2023
Modeling SHANK3-associated autism spectrum disorder in Beagle dogs via CRISPR/Cas9 gene editing
Tian R, Li Y, Zhao H, Lyu W, Zhao J, Wang X, Lu H, Xu H, Ren W, Tan Q, Shi Q, Wang G, Zhang Y, Lai L, Mi J, Jiang Y, Zhang Y. Modeling SHANK3-associated autism spectrum disorder in Beagle dogs via CRISPR/Cas9 gene editing. Molecular Psychiatry 2023, 28: 3739-3750. PMID: 37848710, DOI: 10.1038/s41380-023-02276-9.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderSpectrum disorderNon-human primatesDog-human social interactionsPreclinical studiesBattery of behavioral assaysSocial behavior deficitsASD mouse modelsSocial interactionReduced social interactionCRISPR/Cas9 gene editingGenetic mutant miceNeural circuit mechanismsSocial withdrawalBehavioral findingsPsychiatric disordersBehavioral deficitsHeightened anxietyCanine modelSHANK3 mutationsSHANK3 geneCircuit mechanismsMutant miceMouse modelBehavioral assays
2018
Brain region-specific disruption of Shank3 in mice reveals a dissociation for cortical and striatal circuits in autism-related behaviors
Bey AL, Wang X, Yan H, Kim N, Passman RL, Yang Y, Cao X, Towers AJ, Hulbert SW, Duffney LJ, Gaidis E, Rodriguiz RM, Wetsel WC, Yin HH, Jiang YH. Brain region-specific disruption of Shank3 in mice reveals a dissociation for cortical and striatal circuits in autism-related behaviors. Translational Psychiatry 2018, 8: 94. PMID: 29700290, PMCID: PMC5919902, DOI: 10.1038/s41398-018-0142-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutism Spectrum DisorderBehavior, AnimalCorpus StriatumDisease Models, AnimalExcitatory Postsynaptic PotentialsHippocampusHomer Scaffolding ProteinsMice, KnockoutMicrofilament ProteinsNerve Tissue ProteinsNeuronsPhenotypeProsencephalonReceptors, Dopamine D1Receptors, Dopamine D2Receptors, N-Methyl-D-AspartateSocial BehaviorSynapsesConceptsDeletion of Shank3Brain regionsAutism-related behaviorsWhole-cell patch recordingsGluN2B-containing NMDARsShank3 mutant miceHomer1b/cRegion-specific disruptionRespective brain regionsNeural circuit mechanismsSpecific brain regionsASD-like behaviorsStriatal lossStriatal neuronsElectrophysiological findingsExcitatory neuronsHippocampal neuronsCell type-specific rolesInhibitory neuronsASD-related behaviorsStriatal circuitsSHANK3 deletionStriatal D1Excessive groomingPatch recordings
2016
Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism
Wang X, Bey AL, Katz BM, Badea A, Kim N, David LK, Duffney LJ, Kumar S, Mague SD, Hulbert SW, Dutta N, Hayrapetyan V, Yu C, Gaidis E, Zhao S, Ding JD, Xu Q, Chung L, Rodriguiz RM, Wang F, Weinberg RJ, Wetsel WC, Dzirasa K, Yin H, Jiang YH. Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism. Nature Communications 2016, 7: 11459. PMID: 27161151, PMCID: PMC4866051, DOI: 10.1038/ncomms11459.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutism Spectrum DisorderBehavior, AnimalCerebral CortexCorpus StriatumFemaleHomer Scaffolding ProteinsHumansLong-Term Synaptic DepressionMaleMiceMice, KnockoutMicrofilament ProteinsModels, NeurologicalNerve NetNerve Tissue ProteinsReceptor, Metabotropic Glutamate 5Sequence DeletionSocial BehaviorConceptsASD-like behaviorsCircuit mechanismsStriatal synaptic plasticityAutism spectrum disorderAbnormal brain morphologyPathophysiology of ASDNeural circuit mechanismsHuman neuroimaging studiesKnockout mouse modelAberrant neural connectivityCircuit abnormalitiesStriatal neuronsStriatal synapsesCorticostriatal connectivityBehavioral deficitsAberrant structural connectivityMouse modelThalamic circuitsExcessive groomingSynaptic plasticityBrain morphologyNeuroimaging studiesSHANK3 geneNeural connectivityKnockout models