2019
Maternal valproic acid exposure leads to neurogenesis defects and autism-like behaviors in non-human primates
Zhao H, Wang Q, Yan T, Zhang Y, Xu H, Yu H, Tu Z, Guo X, Jiang Y, Li X, Zhou H, Zhang Y. Maternal valproic acid exposure leads to neurogenesis defects and autism-like behaviors in non-human primates. Translational Psychiatry 2019, 9: 267. PMID: 31636273, PMCID: PMC6803711, DOI: 10.1038/s41398-019-0608-1.Peer-Reviewed Original ResearchConceptsNon-human primatesVPA exposurePrefrontal cortexNeuN-positive mature neuronsGFAP-positive astrocytesValproic acid exposureAutism-like behaviorsAutism spectrum disorderCerebellar external granular layerImpaired social interactionMaternal exposureAntiepileptic drugsExternal granular layerRisk factorsVariable presentationMature neuronsMurine modelRodent modelsEpidemiological studiesAcid exposureNeurogenesis defectsNeuronal precursorsEmbryonic brainNeurodevelopmental defectsSimilar exposureANK2 autism mutation targeting giant ankyrin-B promotes axon branching and ectopic connectivity
Yang R, Walder-Christensen KK, Kim N, Wu D, Lorenzo DN, Badea A, Jiang YH, Yin HH, Wetsel WC, Bennett V. ANK2 autism mutation targeting giant ankyrin-B promotes axon branching and ectopic connectivity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 15262-15271. PMID: 31285321, PMCID: PMC6660793, DOI: 10.1073/pnas.1904348116.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsAnkyrinsAutism Spectrum DisorderBehavior, AnimalCell MembraneConnectomeDisease Models, AnimalExecutive FunctionGene ExpressionGene Knock-In TechniquesHumansMaleMiceMice, TransgenicMicrotubulesMutationNeural Cell Adhesion Molecule L1Neuronal OutgrowthNeuronsPrimary Cell CultureSocial BehaviorSynapses
2018
Epigenetic dysregulation of Oxtr in Tet1-deficient mice has implications for neuropsychiatric disorders
Towers AJ, Tremblay MW, Chung L, Li XL, Bey AL, Zhang W, Cao X, Wang X, Wang P, Duffney LJ, Siecinski SK, Xu S, Kim Y, Kong X, Gregory S, Xie W, Jiang YH. Epigenetic dysregulation of Oxtr in Tet1-deficient mice has implications for neuropsychiatric disorders. JCI Insight 2018, 3: e120592. PMID: 30518695, PMCID: PMC6328031, DOI: 10.1172/jci.insight.120592.Peer-Reviewed Original ResearchCRISPR/Cas9-mediated disruption of SHANK3 in monkey leads to drug-treatable autism-like symptoms
Tu Z, Zhao H, Li B, Yan S, Wang L, Tang Y, Li Z, Bai D, Li C, Lin Y, Li Y, Liu J, Xu H, Guo X, Jiang YH, Zhang YQ, Li XJ. CRISPR/Cas9-mediated disruption of SHANK3 in monkey leads to drug-treatable autism-like symptoms. Human Molecular Genetics 2018, 28: 561-571. PMID: 30329048, PMCID: PMC6489410, DOI: 10.1093/hmg/ddy367.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderCynomolgus monkey modelAutism-like symptomsPathogenesis of ASDPostsynaptic scaffold proteinsNon-human primatesFluoxetine treatmentBrain network activityMonkey modelMouse modelBehavioral abnormalitiesCausative roleExperimental therapeuticsSHANK3 mutationsBrain structuresSHANK3 geneTranslational researchMonogenic mutationsBrain activitySpecies-dependent differencesPositron emissionNetwork activityCRISPR/Cas9-mediated disruptionMonkeysSpectrum disorderEarly Correction of N-Methyl-D-Aspartate Receptor Function Improves Autistic-like Social Behaviors in Adult Shank2 −/− Mice
Chung C, Ha S, Kang H, Lee J, Um SM, Yan H, Yoo YE, Yoo T, Jung H, Lee D, Lee E, Lee S, Kim J, Kim R, Kwon Y, Kim W, Kim H, Duffney L, Kim D, Mah W, Won H, Mo S, Kim JY, Lim CS, Kaang BK, Boeckers TM, Chung Y, Kim H, Jiang YH, Kim E. Early Correction of N-Methyl-D-Aspartate Receptor Function Improves Autistic-like Social Behaviors in Adult Shank2 −/− Mice. Biological Psychiatry 2018, 85: 534-543. PMID: 30466882, PMCID: PMC6420362, DOI: 10.1016/j.biopsych.2018.09.025.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderSocial behaviorSpectrum disorderAutistic-like phenotypesLate pathophysiologyNMDAR hypofunctionHuman autism spectrum disorderNMDAR hyperfunctionN-methyl-D-aspartate (NMDA) receptor hypofunctionAutistic-like behaviorsNMDAR antagonist memantineAspartate Receptor FunctionEarly pathophysiologyPup stageEarly correctionAdult miceBehavioral analysisNMDAR dysfunctionPostnatal day 21Receptor hypofunctionChronic suppressionAnimal studiesDay 21HypofunctionDisordersBrain 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 recordingsModeling autism in non‐human primates: Opportunities and challenges
Zhao H, Jiang Y, Zhang YQ. Modeling autism in non‐human primates: Opportunities and challenges. Autism Research 2018, 11: 686-694. PMID: 29573234, PMCID: PMC6188783, DOI: 10.1002/aur.1945.Peer-Reviewed Original Research
2017
Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers
Pappas A, Bey A, Wang X, Rossi M, Kim Y, Yan H, Porkka F, Duffney L, Phillips S, Cao X, Ding J, Rodriguiz R, Yin H, Weinberg R, Ji R, Wetsel W, Jiang Y. Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers. JCI Insight 2017, 2: e92052. PMID: 29046483, PMCID: PMC5846902, DOI: 10.1172/jci.insight.92052.Peer-Reviewed Original ResearchAmphetamineAnhedoniaAnimalsAntimanic AgentsBehavior, AnimalBipolar DisorderCentral Nervous System StimulantsChronobiology DisordersCognitive DysfunctionFemaleHippocampusLithium CompoundsMaleMiceMice, KnockoutMotor ActivityNerve Tissue ProteinsN-MethylaspartatePhenotypeProsencephalonReceptors, AMPAReceptors, N-Methyl-D-AspartateSocial Behavior DisordersSynapses
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
2014
Overview of Mouse Models of Autism Spectrum Disorders
Bey AL, Jiang Y. Overview of Mouse Models of Autism Spectrum Disorders. Current Protocols In Pharmacology 2014, 66: 5.66.1-5.66.26. PMID: 25181011, PMCID: PMC4186887, DOI: 10.1002/0471141755.ph0566s66.Peer-Reviewed Original Research
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
2007
Rescue of neurological deficits in a mouse model for Angelman syndrome by reduction of αCaMKII inhibitory phosphorylation
van Woerden GM, Harris KD, Hojjati MR, Gustin RM, Qiu S, de Avila Freire R, Jiang YH, Elgersma Y, Weeber EJ. Rescue of neurological deficits in a mouse model for Angelman syndrome by reduction of αCaMKII inhibitory phosphorylation. Nature Neuroscience 2007, 10: 280-282. PMID: 17259980, DOI: 10.1038/nn1845.Peer-Reviewed Original ResearchMeSH KeywordsAngelman SyndromeAnimalsBehavior, AnimalCalcium-Calmodulin-Dependent Protein Kinase Type 2Conditioning, ClassicalDisease Models, AnimalExcitatory Postsynaptic PotentialsFemaleFreezing Reaction, CatalepticHippocampusIn Vitro TechniquesMaleMaze LearningMental DisordersMiceMice, Inbred C57BLMice, Neurologic MutantsMotor ActivityPhosphorylationPhosphotransferasesReaction TimeTime FactorsUbiquitin-Protein LigasesConceptsMouse modelAngelman syndromeAS mouse modelSevere neurological disordersNeurological deficitsMotor dysfunctionA miceBehavioral deficitsCellular deficitsNeurological disordersInhibitory phosphorylationMental retardationSyndromeDeficitsΑCaMKIIAdditional mutationsInhibitory phosphorylation sites