2024
Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs
Zhu F, Shi Q, Jiang Y, Zhang Y, Zhao H. Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs. Molecular Autism 2024, 15: 9. PMID: 38297387, PMCID: PMC10829216, DOI: 10.1186/s13229-024-00587-4.Peer-Reviewed Original ResearchConceptsPrefrontal cortexPyramidal neuronsSHANK3 mutationsPrefrontal cortex neuronal activityPrefrontal cortex pyramidal neuronsSocial behaviorBrain slicesPrefrontal cortex's roleSynaptic transmissionPrefrontal cortex layersStudy social cognitionAutism spectrum disorderAutism-like behaviorsDendritic spine morphologyReduced dendritic complexitySocial cognitionSocial impairmentBehavioral alterationsNeural mechanismsExcitatory synaptic transmissionMutant rodent modelsHeightened anxietySpectrum disorderSpine densityImpaired synaptic function
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
2021
Psychometric properties of the Chinese Parent Version of the Autism Spectrum Rating Scale: Rasch analysis
Yan W, Siegert RJ, Zhou H, Zou X, Wu L, Luo X, Li T, Huang Y, Guan H, Chen X, Mao M, Xia K, Zhang L, Li E, Li C, Zhang X, Zhou Y, Shih A, Fombonne E, Zheng Y, Han J, Sun Z, Jiang YH, Wang Y. Psychometric properties of the Chinese Parent Version of the Autism Spectrum Rating Scale: Rasch analysis. Autism 2021, 25: 1872-1884. PMID: 33845648, PMCID: PMC8548063, DOI: 10.1177/13623613211004054.Peer-Reviewed Original ResearchMeSH KeywordsAutism Spectrum DisorderAutistic DisorderChildChinaHumansParentsPsychometricsReproducibility of ResultsConceptsAutism Spectrum Rating ScaleAutism spectrum disorderSpectrum disorderRasch analysisRating ScaleBehavioral rating scalesIdentification of childrenParent versionRasch measurementPsychometric propertiesChinese childrenChildrenDisordersParentsSupport servicesScaleStringent criteriaItemsGrandparentsScientific measurementsQuestionnaireBehavior characteristicsTeachers
2020
The role of Hipk2-p53 pathways in arsenic-induced autistic behaviors: A translational study from rats to humans
Zhou H, Lin Y, Zhao W, Teng Y, Cui Y, Wang T, Li C, Jiang YH, Zhang JJ, Wang Y. The role of Hipk2-p53 pathways in arsenic-induced autistic behaviors: A translational study from rats to humans. Environmental Pollution 2020, 267: 115568. PMID: 33254717, DOI: 10.1016/j.envpol.2020.115568.Peer-Reviewed Original ResearchConceptsCase-control studySerum levelsArsenic exposureHealthy controlsNeuronal apoptosisFrontal cortexAge-matched healthy controlsGestational arsenic exposureHuman case-control studiesASD developmentHigher serum levelsAutistic behaviorASD childrenDose-dependent mannerAutism spectrum disorderPotential mediating pathwaysRat modelRat pupsKey molecular changesImmunohistochemistry analysisTranslational studiesWestern blottingMolecular changesTranslational strategiesMediating pathwaysA Novel Chd8 Mutant Mouse Displays Altered Ultrasonic Vocalizations and Enhanced Motor Coordination
Hulbert SW, Wang X, Gbadegesin SO, Xu Q, Xu X, Jiang Y. A Novel Chd8 Mutant Mouse Displays Altered Ultrasonic Vocalizations and Enhanced Motor Coordination. Autism Research 2020, 13: 1685-1697. PMID: 32815320, PMCID: PMC7780289, DOI: 10.1002/aur.2353.Peer-Reviewed Original Research
2018
Autism-associated CHD8 deficiency impairs axon development and migration of cortical neurons
Xu Q, Liu YY, Wang X, Tan GH, Li HP, Hulbert SW, Li CY, Hu CC, Xiong ZQ, Xu X, Jiang YH. Autism-associated CHD8 deficiency impairs axon development and migration of cortical neurons. Molecular Autism 2018, 9: 65. PMID: 30574290, PMCID: PMC6299922, DOI: 10.1186/s13229-018-0244-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutistic DisorderCells, CulturedCerebral CortexDNA-Binding ProteinsHumansMiceMice, Inbred C57BLNeurogenesisNeuronsConceptsCHD8 deficiencyNeuronal migrationChromodomain helicase DNAMouse brainChromatin structureTranscriptional regulatorsParvalbumin-positive neuronsHistone H1Autism spectrum disorderGenetic studiesCHD8Protein 8Functional consequencesNovel insightsBiochemical analysisContralateral cortexSitu hybridizationCortical neuronsCommon findingUtero electroporationGlia cellsNeuronal culturesAxon projectionsDeficiency impairsCircuit mechanismsEpigenetics and autism spectrum disorder: A report of an autism case with mutation in H1 linker histone HIST1H1E and literature review
Duffney LJ, Valdez P, Tremblay MW, Cao X, Montgomery S, McConkie‐Rosell A, Jiang Y. Epigenetics and autism spectrum disorder: A report of an autism case with mutation in H1 linker histone HIST1H1E and literature review. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2018, 177: 426-433. PMID: 29704315, PMCID: PMC5980735, DOI: 10.1002/ajmg.b.32631.Peer-Reviewed Original ResearchConceptsLinker proteinH1 linker histonesLinker histone proteinFamily member EChromatin organizationEpigenetic machineryHistone proteinsEpigenetic regulationLinker histonesNucleosome packagingLoss of functionDeleterious mutationsCandidate genesExpression studiesHistone writersWhole-exome sequencingHuman diseasesGenesProteinMutationsProtein expressionExome sequencingGenetic mutationsMember EHIST1H1ESystematic reconstruction of autism biology from massive genetic mutation profiles
Luo W, Zhang C, Jiang YH, Brouwer CR. Systematic reconstruction of autism biology from massive genetic mutation profiles. Science Advances 2018, 4: e1701799. PMID: 29651456, PMCID: PMC5895441, DOI: 10.1126/sciadv.1701799.Peer-Reviewed Original ResearchConceptsComplex genetic diseasesWhole-exome studiesHundreds of variantsGene functionNovel genesSubpathway levelGene groupsSame geneCanonical pathwaysPathway levelAutism-related mutationsSecond messenger systemsGenesGenetic diseasesASD biologyCAMP second messenger systemBiologyGenetic associationMutationsMultiple independent analysesMost variantsPathwayVariant levelsSynaptic functionGenetic mutation profilesCRISPR/Cas9-induced shank3b mutant zebrafish display autism-like behaviors
Liu CX, Li CY, Hu CC, Wang Y, Lin J, Jiang YH, Li Q, Xu X. CRISPR/Cas9-induced shank3b mutant zebrafish display autism-like behaviors. Molecular Autism 2018, 9: 23. PMID: 29619162, PMCID: PMC5879542, DOI: 10.1186/s13229-018-0204-x.Peer-Reviewed Original ResearchConceptsMutant zebrafishMutant zebrafish modelGenome editing techniquesGene editing approachesZebrafish genomeOrthologous genesAttractive organismGenomic studiesCRISPR/Cas9 gene editing approachGenetic manipulationZebrafish modelCRISPR/ZebrafishMolecular mechanismsEditing approachesAdult stageFunction mutationsMolecular analysisEditing techniquesMolecular changesAutism-like behaviorsEarly developmentSwimming behaviorPresynaptic synaptophysinMorphological measurements
2017
Cellular and Circuitry Bases of Autism: Lessons Learned from the Temporospatial Manipulation of Autism Genes in the Brain
Hulbert SW, Jiang YH. Cellular and Circuitry Bases of Autism: Lessons Learned from the Temporospatial Manipulation of Autism Genes in the Brain. Neuroscience Bulletin 2017, 33: 205-218. PMID: 28271437, PMCID: PMC5360850, DOI: 10.1007/s12264-017-0112-7.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderDifferent neurotransmitter systemsCell typesNeurotransmitter systemsInhibitory neuronsAdult miceTransgenic miceBrain regionsCre linesDevelopmental time periodCre-loxPCertain cell typesMiceCore ASD symptomsDisordersMolecular underpinningsTime periodSpectrum disorderASD symptomsGene expressionMutations
2016
Chromosomal microarray analysis in clinical evaluation of neurodevelopmental disorders-reporting a novel deletion of SETDB1 and illustration of counseling challenge
Xu Q, Goldstein J, Wang P, Gadi IK, Labreche H, Rehder C, Wang WP, McConkie A, Xu X, Jiang YH. Chromosomal microarray analysis in clinical evaluation of neurodevelopmental disorders-reporting a novel deletion of SETDB1 and illustration of counseling challenge. Pediatric Research 2016, 80: 371-381. PMID: 27119313, PMCID: PMC5382808, DOI: 10.1038/pr.2016.101.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAlgorithmsAutistic DisorderChildChild, PreschoolChromatinComparative Genomic HybridizationCounselingDevelopmental DisabilitiesDNA Copy Number VariationsFemaleGene DeletionGene RearrangementHistone-Lysine N-MethyltransferaseHumansInfantIntellectual DisabilityMaleMicroarray AnalysisNeurodevelopmental DisordersPedigreeProtein MethyltransferasesConceptsNeurodevelopmental disordersAutism spectrum disorderIntellectual disabilityDevelopmental disabilitiesCopy number variationsChromosomal microarray analysisEtiological evaluationClinical evaluationClinical significanceUnknown significanceCNV analysisGenetics clinicEtiology of ASDCounseling familiesDisordersVariable penetranceClinicMicroarray analysisNovel deletionSpectrum disorderDisabilityCounseling challengesFurther supportEtiologyCohort
2014
A CACNA1C Variant Associated with Reduced Voltage-Dependent Inactivation, Increased CaV1.2 Channel Window Current, and Arrhythmogenesis
Hennessey JA, Boczek NJ, Jiang YH, Miller JD, Patrick W, Pfeiffer R, Sutphin BS, Tester DJ, Barajas-Martinez H, Ackerman MJ, Antzelevitch C, Kanter R, Pitt GS. A CACNA1C Variant Associated with Reduced Voltage-Dependent Inactivation, Increased CaV1.2 Channel Window Current, and Arrhythmogenesis. PLOS ONE 2014, 9: e106982. PMID: 25184293, PMCID: PMC4153713, DOI: 10.1371/journal.pone.0106982.Peer-Reviewed Original ResearchMeSH KeywordsAutistic DisorderCalcium Channels, L-TypeChild, PreschoolFemaleHumansInfantLong QT SyndromeMaleMembrane PotentialsMutationSyndactylyConceptsSudden unexplained infant deathVoltage-dependent inactivationLong QT syndromeWindow currentTimothy syndromeCav1.2 L-type Ca2Multiple dental cariesLower extremity weaknessGain of functionCertain clinical settingsEpisodes of rhabdomyolysisUnexplained infant deathL-type Ca2Channel window currentAge 5 yearsYears of ageAppreciation of mechanismsMonths of ageCandidate gene sequencingCardiac ion channelsRecurrent VTExtremity weaknessSpastic diplegiaExtracardiac featuresDental cariesOverview 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
2013
Modeling Autism by SHANK Gene Mutations in Mice
Jiang YH, Ehlers MD. Modeling Autism by SHANK Gene Mutations in Mice. Neuron 2013, 78: 8-27. PMID: 23583105, PMCID: PMC3659167, DOI: 10.1016/j.neuron.2013.03.016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutistic DisorderDisease Models, AnimalHumansMiceModels, MolecularMutationNerve Tissue ProteinsPost-Synaptic DensityConceptsSHANK mutationsRecent human genetic studiesSHANK family genesHuman genetic studiesPostsynaptic densityPathophysiology of ASDProtein complexesConserved featuresFamily genesFamily proteinsGene productsDivergent phenotypesSame geneExcitatory glutamatergic synapsesMolecular diversityHuman autism spectrum disorderMouse mutantsMolecular geneticsGenetic studiesMouse phenotypeSynaptic dysfunctionIdiopathic autism spectrum disorderSuch mutationsCausative genesGenes
2012
Mutations of ANK3 identified by exome sequencing are associated with autism susceptibility
Bi C, Wu J, Jiang T, Liu Q, Cai W, Yu P, Cai T, Zhao M, Jiang Y, Sun ZS. Mutations of ANK3 identified by exome sequencing are associated with autism susceptibility. Human Mutation 2012, 33: 1635-1638. PMID: 22865819, DOI: 10.1002/humu.22174.Peer-Reviewed Original ResearchConceptsExtensive bioinformatics analysisNext-generation sequencing technologiesExtreme genetic heterogeneityStrong genetic etiologyGene discoveryWhole-exome sequencesDifferent missense mutationsBioinformatics analysisSequencing technologiesAutism susceptibilityMissense mutationsANK3Genetic heterogeneityMutationsNovo mutationsExome sequencingMolecular pathophysiologyGenetic causeGenetic etiologyASD susceptibilitySynaptic functionNovel mutationsNeurodevelopmental disordersGenesSequencing
2004
A mixed epigenetic/genetic model for oligogenic inheritance of autism with a limited role for UBE3A
Jiang Y, Sahoo T, Michaelis RC, Bercovich D, Bressler J, Kashork CD, Liu Q, Shaffer LG, Schroer RJ, Stockton DW, Spielman RS, Stevenson RE, Beaudet AL. A mixed epigenetic/genetic model for oligogenic inheritance of autism with a limited role for UBE3A. American Journal Of Medical Genetics Part A 2004, 131A: 1-10. PMID: 15389703, DOI: 10.1002/ajmg.a.30297.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAutistic DisorderBlotting, SouthernBlotting, WesternBrainChromosome AberrationsChromosomes, Human, Pair 15Deoxyribonuclease BamHIDeoxyribonuclease HpaIIDNADNA MethylationFemaleGene DuplicationHumansIn Situ Hybridization, FluorescenceMaleModels, GeneticMutationPedigreeUbiquitin-Protein LigasesConceptsOligogenic inheritanceComplex disease traitsGenome-wide studiesAbnormal DNA methylationE6-AP proteinDe novoGenetic modelsRole of UBE3AUbiquitin ligaseDNA methylationEpigenetic abnormalitiesDisease traitsAutism brainPaternal duplicationChromosome 15qUBE3AGenetic contributionRegion downstreamGenesOligogenic modelInheritanceProteinNovoLigaseBrain samplesAutism as a disorder of neural information processing: directions for research and targets for therapy
Belmonte MK, Cook EH, Anderson GM, Rubenstein JL, Greenough WT, Beckel-Mitchener A, Courchesne E, Boulanger LM, Powell SB, Levitt PR, Perry EK, Jiang YH, DeLorey TM, Tierney E. Autism as a disorder of neural information processing: directions for research and targets for therapy. Molecular Psychiatry 2004, 9: 646-663. PMID: 15037868, DOI: 10.1038/sj.mp.4001499.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderNormal developmental courseNeural information processingBrain developmentSpectrum disorderBehavioral findingsDevelopmental courseComplex behavioral syndromeNeural systemsInformation processingAutismBehavioral manipulationMultiple predisposing factorsDevelopmental pathCommon developmental pathNeural propertiesCausal factorsBehavioral syndromeAbnormal brain developmentDevelopmental processesCognitionActivity-dependent developmentDisordersComplex waysEndophenotypes