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
2022
Inhibition 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 ResearchConceptsAcute 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
2019
Potassium channel dysfunction in human neuronal models of Angelman syndrome
Sun A, Yuan Q, Fukuda M, Yu W, Yan H, Lim G, Nai M, D'Agostino G, Tran H, Itahana Y, Wang D, Lokman H, Itahana K, Lim S, Tang J, Chang Y, Zhang M, Cook S, Rackham O, Lim C, Tan E, Ng H, Lim K, Jiang Y, Je H. Potassium channel dysfunction in human neuronal models of Angelman syndrome. Science 2019, 366: 1486-1492. PMID: 31857479, PMCID: PMC7735558, DOI: 10.1126/science.aav5386.Peer-Reviewed Original ResearchConceptsAngelman syndromePotassium channel dysfunctionAS mouse modelUbiquitin protein ligase E3A (UBE3A) geneHuman neuronal modelNeuronal hyperexcitabilityNetwork hyperactivityAS patientsSeizure susceptibilitySynaptic dysfunctionModel miceIntrinsic excitabilityNeuronal excitabilityMouse modelBig potassium channelsHuman neuronsChannel dysfunctionEpilepsy susceptibilityBK channelopathyMouse neuronsPotassium channelsIndividual neuronsBrain organoidsNeuronsDysfunction
2018
CRISPR/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 disorderEnvironmental 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 Research
2017
Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model
Chung L, Bey AL, Towers AJ, Cao X, Kim IH, Jiang YH. Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model. Neurobiology Of Disease 2017, 110: 12-19. PMID: 29097328, PMCID: PMC5903876, DOI: 10.1016/j.nbd.2017.10.016.Peer-Reviewed Original ResearchConceptsEpileptiform activityMouse modelAngelman syndrome modelFragile X syndrome mouse modelLower seizure thresholdSyndrome mouse modelNeural mechanismsAngelman syndromeSeizure thresholdSynaptic dysfunctionAudiogenic seizuresExcitatory neurotransmissionLocal circuitsSyndrome modelSeizuresUBE3ADrug screeningFXS modelsHyperexcitabilitySupDysfunctionEpilepsyNeurotransmissionSyndromeDissection
2016
Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of Prader–Willi syndrome
Kim Y, Lee HM, Xiong Y, Sciaky N, Hulbert SW, Cao X, Everitt JI, Jin J, Roth BL, Jiang YH. Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of Prader–Willi syndrome. Nature Medicine 2016, 23: 213-222. PMID: 28024084, PMCID: PMC5589073, DOI: 10.1038/nm.4257.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCell LineDisease Models, AnimalEnzyme InhibitorsEpigenesis, GeneticFemaleFibroblastsGene ExpressionGenomic ImprintingHistone CodeHistone-Lysine N-MethyltransferaseHumansImmunohistochemistryMaleMethylationMicePrader-Willi SyndromeQuinazolinesReverse Transcriptase Polymerase Chain ReactionRNA, Small NucleolarSnRNP Core ProteinsSurvival RateUbiquitin-Protein LigasesAltered 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
2013
Region‐specific impairments in striatal synaptic transmission and impaired instrumental learning in a mouse model of Angelman syndrome
Hayrapetyan V, Castro S, Sukharnikova T, Yu C, Cao X, Jiang YH, Yin HH. Region‐specific impairments in striatal synaptic transmission and impaired instrumental learning in a mouse model of Angelman syndrome. European Journal Of Neuroscience 2013, 39: 1018-1025. PMID: 24329862, PMCID: PMC5937017, DOI: 10.1111/ejn.12442.Peer-Reviewed Original ResearchConceptsDorsolateral striatumDorsomedial striatumMouse modelAngelman syndromeWhole-cell patch-clamp recordingsMiniature excitatory postsynaptic currentsRegion-specific impairmentsStriatal synaptic transmissionExcitatory postsynaptic currentsBasal ganglia pathologyPatch-clamp recordingsDeficient mouse modelUbe3a deficiencyWild-type controlsGlutamatergic transmissionPostsynaptic currentsBasal gangliaSynaptic transmissionInput nucleusMaternal deficiencyMotor tremorCorticostriatal circuitsMutant miceStriatumMiceThe Angelman Syndrome Protein Ube3a Is Required for Polarized Dendrite Morphogenesis in Pyramidal Neurons
Miao S, Chen R, Ye J, Tan G, Li S, Zhang J, Jiang Y, Xiong Z. The Angelman Syndrome Protein Ube3a Is Required for Polarized Dendrite Morphogenesis in Pyramidal Neurons. Journal Of Neuroscience 2013, 33: 327-333. PMID: 23283345, PMCID: PMC6618628, DOI: 10.1523/jneurosci.2509-12.2013.Peer-Reviewed Original ResearchConceptsPyramidal neuronsApical dendritesLong apical dendritesNeuron dendritic arborsDendrite outgrowthUbiquitin protein ligase E3ANovel pathological mechanismBasal dendritesCorticospinal tractDendritic arborsMouse modelPathological mechanismsMammalian prefrontal cortexExcitatory cellsPrefrontal cortexNeuronsDendrite morphogenesisCellular mechanismsDendritic morphologySelective inhibitionUBE3AMiceDendritesMolecular mechanismsDownregulation
2012
Synaptic Plasticity in Mouse Models of Autism Spectrum Disorders
Chung L, Bey AL, Jiang YH. Synaptic Plasticity in Mouse Models of Autism Spectrum Disorders. Korean Journal Of Physiology And Pharmacology 2012, 16: 369-378. PMID: 23269898, PMCID: PMC3526740, DOI: 10.4196/kjpp.2012.16.6.369.Peer-Reviewed Original ResearchSynaptic plasticityAutism spectrum disorderConditional mutant miceSpectrum disorderHuman autism spectrum disorderMouse modelTherapeutic targetBehavioral abnormalitiesSynaptic defectsVisual cortexMutant miceNeuroanatomical basisDisordersAutistic behaviorAbnormalitiesMiceConstruct validitySubject of debateMost studiesMolecular studiesCore featuresCommon regionHippocampusCortexPlasticity
2010
Altered Ultrasonic Vocalization and Impaired Learning and Memory in Angelman Syndrome Mouse Model with a Large Maternal Deletion from Ube3a to Gabrb3
Jiang YH, Pan Y, Zhu L, Landa L, Yoo J, Spencer C, Lorenzo I, Brilliant M, Noebels J, Beaudet AL. Altered Ultrasonic Vocalization and Impaired Learning and Memory in Angelman Syndrome Mouse Model with a Large Maternal Deletion from Ube3a to Gabrb3. PLOS ONE 2010, 5: e12278. PMID: 20808828, PMCID: PMC2924885, DOI: 10.1371/journal.pone.0012278.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAngelman SyndromeAnimalsCerebral CortexChromosome DeletionDarknessDisease Models, AnimalExploratory BehaviorFemaleGene Expression RegulationHomozygoteMaleMembrane Transport ProteinsMemoryMiceMothersMotor ActivityReceptors, GABA-ASeizuresUbiquitin-Protein LigasesUltrasonicsVocalization, AnimalConceptsLarge maternal deletionsDeletion miceMutant miceMouse modelAngelman syndrome mouse modelAngelman syndromeSpontaneous seizure activityMaternal deletionAS mouse modelGABRB3 geneWild-type littermatesSyndrome mouse modelE6-AP ubiquitinLight-dark boxDeletion mutant miceUBE3A mutationsUniparental disomyElectroencephalography (EEG) abnormalitiesAS patientsAbnormal EEGSeizure activityMotor functionPerinatal periodBalance disordersPaternal uniparental disomy
2009
Mitochondrial dysfunction in CA1 hippocampal neurons of the UBE3A deficient mouse model for Angelman syndrome
Su H, Fan W, Coskun PE, Vesa J, Gold JA, Jiang YH, Potluri P, Procaccio V, Acab A, Weiss JH, Wallace DC, Kimonis VE. Mitochondrial dysfunction in CA1 hippocampal neurons of the UBE3A deficient mouse model for Angelman syndrome. Neuroscience Letters 2009, 487: 129-133. PMID: 19563863, PMCID: PMC2888840, DOI: 10.1016/j.neulet.2009.06.079.Peer-Reviewed Original ResearchConceptsWild-type littermatesAngelman syndromeMaternal UBE3A alleleMitochondrial dysfunctionCA1 hippocampal neuronsSynaptic vesicle densityWhole brain mitochondriaDeficient mouse modelUbiquitin protein ligase E3ASevere neurological disordersAS miceHippocampal neuronsHippocampal regionMouse modelOxidative phosphorylationNeurological disordersBrain mitochondriaSyndromeMiceVesicle densityPathophysiologyDysfunctionDense mitochondriaLittermatesUBE3A
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
2003
Derangements of Hippocampal Calcium/Calmodulin-Dependent Protein Kinase II in a Mouse Model for Angelman Mental Retardation Syndrome
Weeber EJ, Jiang YH, Elgersma Y, Varga AW, Carrasquillo Y, Brown SE, Christian JM, Mirnikjoo B, Silva A, Beaudet AL, Sweatt JD. Derangements of Hippocampal Calcium/Calmodulin-Dependent Protein Kinase II in a Mouse Model for Angelman Mental Retardation Syndrome. Journal Of Neuroscience 2003, 23: 2634-2644. PMID: 12684449, PMCID: PMC6742065, DOI: 10.1523/jneurosci.23-07-02634.2003.Peer-Reviewed Original ResearchMeSH KeywordsAngelman SyndromeAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein KinasesCells, CulturedHippocampusImmunohistochemistryIntellectual DisabilityLigasesLong-Term PotentiationMiceMutationPhosphoprotein PhosphatasesPhosphorylationProtein KinasesSynapsesThreonineUbiquitin-Protein LigasesConceptsCalmodulin-dependent protein kinase IIProtein kinase IIKinase IIAngelman syndromeCalcium/calmodulin-dependent protein kinase IIMutant animalsMolecular basisMental retardation syndromeMolecular causesCaMKII activityLong-term potentiationCaMKIIPostsynaptic densityRetardation syndromeMouse modelMisregulationMutantsHippocampal long-term potentiationSevere mental retardationMental retardationContext-dependent learningCorresponding changes