2021
Mutations of the histone linker H1–4 in neurodevelopmental disorders and functional characterization of neurons expressing C-terminus frameshift mutant H1.4
Tremblay MW, Green MV, Goldstein BM, Aldridge AI, Rosenfeld JA, Streff H, Tan WD, Craigen W, Bekheirnia N, Al Tala S, West AE, Jiang YH. Mutations of the histone linker H1–4 in neurodevelopmental disorders and functional characterization of neurons expressing C-terminus frameshift mutant H1.4. Human Molecular Genetics 2021, 31: 1430-1442. PMID: 34788807, PMCID: PMC9271223, DOI: 10.1093/hmg/ddab321.Peer-Reviewed Original ResearchConceptsC-terminusGenome-wide transcriptome analysisRahman syndromeUnderstanding of mutationsHistone H1.4Neuronal genesTranscriptome analysisAbnormal C-terminusFunctional categoriesFunctional characterizationNeuropeptide signalingN-terminusDe novo heterozygous mutationsSupport of pathogenicitySmall insertionsFunctional consequencesNovo heterozygous mutationRat hippocampal neuronsFrameshift mutationMutationsH1.4Rare genetic disorderSevere intellectual disabilityGenesClinical features
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 organoidsNeuronsDysfunctionNeurodevelopmental mutation of giant ankyrin-G disrupts a core mechanism for axon initial segment assembly
Yang R, Walder-Christensen KK, Lalani S, Yan H, García-Prieto ID, Álvarez S, Fernández-Jaén A, Speltz L, Jiang YH, Bennett V. Neurodevelopmental mutation of giant ankyrin-G disrupts a core mechanism for axon initial segment assembly. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 19717-19726. PMID: 31451636, PMCID: PMC6765234, DOI: 10.1073/pnas.1909989116.Peer-Reviewed Original ResearchConceptsΒ4-spectrinAxon initial segmentC-terminal domainNormal neural developmentPrevents recruitmentGiant ankyrinNeural developmentConformational changesMissense mutationsMutationsPhosphorylationSegment assemblyRecruitmentMouse brainClose appositionCore mechanismDomainAssemblyAnkyrinClosed configurationIntermediate stageInitial segmentSitesProximal axonsANK2 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
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 ResearchConceptsCHD8 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 mechanismsBrain 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
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
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 miceStriatumMice
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
1998
Mutation of the Angelman Ubiquitin Ligase in Mice Causes Increased Cytoplasmic p53 and Deficits of Contextual Learning and Long-Term Potentiation
Jiang Y, Armstrong D, Albrecht U, Atkins C, Noebels J, Eichele G, Sweatt J, Beaudet A. Mutation of the Angelman Ubiquitin Ligase in Mice Causes Increased Cytoplasmic p53 and Deficits of Contextual Learning and Long-Term Potentiation. Neuron 1998, 21: 799-811. PMID: 9808466, DOI: 10.1016/s0896-6273(00)80596-6.Peer-Reviewed Original ResearchConceptsLong-term potentiationMaternal deficiencyAngelman syndromeNormal baseline synaptic transmissionBaseline synaptic transmissionE6-AP ubiquitinMotor dysfunctionSynaptic transmissionPhenotype of miceMice causesPotential biochemical basisPostmitotic neuronsLearning deficitsMiceDegradation of p53E6 proteinPotentiationP53Cytoplasmic p53UBE3ACytoplasmic abundanceDeficitsDeficiencyPhenotypeBiochemical basis