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 ResearchMeSH KeywordsAnimalsAutism Spectrum DisorderCRISPR-Cas SystemsDisease Models, AnimalDogsGene EditingHumansMicrofilament ProteinsNerve Tissue ProteinsConceptsAutism 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 assaysSHANK3 in vagal sensory neurons regulates body temperature, systemic inflammation, and sepsis
Zhang L, Bang S, He Q, Matsuda M, Luo X, Jiang Y, Ji R. SHANK3 in vagal sensory neurons regulates body temperature, systemic inflammation, and sepsis. Frontiers In Immunology 2023, 14: 1124356. PMID: 36845137, PMCID: PMC9944123, DOI: 10.3389/fimmu.2023.1124356.Peer-Reviewed Original ResearchConceptsVagal sensory neuronsNodose ganglionSensory neuronsSystemic inflammationBody temperatureDorsal root ganglion sensory neuronsSerum IL-6 levelsAuricular vagus nerve stimulationBasal core temperatureIL-6 levelsVagus nerve stimulationAutism spectrum disorderRole of Shank3Conditional knockout miceSynaptic scaffolding proteinsSepsis mortalityNerve stimulationExcessive inflammationHeat painInflammation dysregulationKO miceKnockout miceInflammationSHANK3 expressionNovel molecular mechanism
2022
Neural circuit pathology driven by Shank3 mutation disrupts social behaviors
Kim S, Kim YE, Song I, Ujihara Y, Kim N, Jiang YH, Yin HH, Lee TH, Kim IH. Neural circuit pathology driven by Shank3 mutation disrupts social behaviors. Cell Reports 2022, 39: 110906. PMID: 35675770, PMCID: PMC9210496, DOI: 10.1016/j.celrep.2022.110906.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutism Spectrum DisorderDisease Models, AnimalHumansMiceMicrofilament ProteinsMutationNerve Tissue ProteinsOptogeneticsPrefrontal CortexSocial BehaviorConceptsAutism spectrum disorderAlters spine morphologyWild-type miceExcitatory-inhibitory balanceSocial dysfunctionHuman ASD patientsMultiple brain regionsSocial behaviorElevated neural activityCircuit pathologyPathogenic mechanismsSHANK3 mutationsCircuit inhibitionBrain regionsCircuit activationNeural network mechanismReduced sociabilitySpine morphologyCore symptomsASD patientsPrefrontal cortexMiceSHANK3 geneNeural activitySpectrum disorderInhibition of Trpv4 rescues circuit and social deficits unmasked by acute inflammatory response in a Shank3 mouse model of Autism
Tzanoulinou S, Musardo S, Contestabile A, Bariselli S, Casarotto G, Magrinelli E, Jiang YH, Jabaudon D, Bellone C. Inhibition of Trpv4 rescues circuit and social deficits unmasked by acute inflammatory response in a Shank3 mouse model of Autism. Molecular Psychiatry 2022, 27: 2080-2094. PMID: 35022531, PMCID: PMC9126815, DOI: 10.1038/s41380-021-01427-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutism Spectrum DisorderAutistic DisorderDisease Models, AnimalHumansMiceMicrofilament ProteinsNerve Tissue ProteinsSocial BehaviorTRPV Cation ChannelsConceptsAcute inflammatory responseInflammatory responseSHANK3 geneTransient receptor potential vanilloid 4Shank3 mouse modelAutism spectrum disorderGenetic risk factorsInhibition of TRPV4Ex vivo approachNeuron hyperexcitabilityRisk factorsBehavioral deficitsNucleus accumbensMouse modelTRPV4 inhibitionBehavioral alterationsSocial deficitsSHANK3 mutationsCircuit mechanismsNeurodevelopmental diseasesGenetic alterationsTypes of mutationsHeterozygous deletionIdiopathic autismEnvironmental insults
2018
Environmental enrichment has minimal effects on behavior in the Shank3 complete knockout model of autism spectrum disorder
Hulbert SW, Bey AL, Jiang Y. Environmental enrichment has minimal effects on behavior in the Shank3 complete knockout model of autism spectrum disorder. Brain And Behavior 2018, 8: e01107. PMID: 30317697, PMCID: PMC6236244, DOI: 10.1002/brb3.1107.Peer-Reviewed Original ResearchBrain 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
SHANK3 Deficiency Impairs Heat Hyperalgesia and TRPV1 Signaling in Primary Sensory Neurons
Han Q, Kim YH, Wang X, Liu D, Zhang ZJ, Bey AL, Lay M, Chang W, Berta T, Zhang Y, Jiang YH, Ji RR. SHANK3 Deficiency Impairs Heat Hyperalgesia and TRPV1 Signaling in Primary Sensory Neurons. Neuron 2016, 92: 1279-1293. PMID: 27916453, PMCID: PMC5182147, DOI: 10.1016/j.neuron.2016.11.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalBlotting, WesternCapsaicinGanglia, SpinalHumansHyperalgesiaImmunohistochemistryInflammationMiceMice, KnockoutMicrofilament ProteinsNAV1.8 Voltage-Gated Sodium ChannelNerve Tissue ProteinsNeuralgiaPainPatch-Clamp TechniquesPresynaptic TerminalsReverse Transcriptase Polymerase Chain ReactionSensory Receptor CellsSensory System AgentsSpinal CordTRPV Cation ChannelsConceptsHeat hyperalgesiaSensory neuronsDRG neuronsMouse dorsal root ganglion sensory neuronsDorsal root ganglion sensory neuronsCapsaicin-induced spontaneous painAbnormal pain sensitivityHuman DRG neuronsPrimary sensory neuronsAutism spectrum disorderSpinal cord neuronsSpontaneous painTRPV1 signalingNeuropathic painPain sensitivityPeripheral mechanismsCord neuronsSHANK3 haploinsufficiencyTRPV1 functionPresynaptic terminalsSynaptic currentsPain deficitsSHANK3 deficiencyInward currentsSHANK3 expressionAltered 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
2011
Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3
Wang X, McCoy PA, Rodriguiz RM, Pan Y, Je HS, Roberts AC, Kim CJ, Berrios J, Colvin JS, Bousquet-Moore D, Lorenzo I, Wu G, Weinberg RJ, Ehlers MD, Philpot BD, Beaudet AL, Wetsel WC, Jiang YH. Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Human Molecular Genetics 2011, 20: 3093-3108. PMID: 21558424, PMCID: PMC3131048, DOI: 10.1093/hmg/ddr212.Peer-Reviewed Original ResearchConceptsPostsynaptic densityMajor clinical featuresHomer1b/cRole of Shank3Activity-dependent redistributionAutism spectrum disorderLong-term potentiationHuman ASD patientsSynaptic scaffolding proteinsHomozygous mutant miceClinical featuresMajor isoformsSynaptic dysfunctionAbnormal social behaviorCA1 hippocampusMale miceCognitive dysfunctionSynaptic transmissionExcitatory synapsesDendritic spinesMotor coordinationAMPA receptorsBehavioral abnormalitiesSHANK3 mutationsSevere impairment