2022
Disrupted Topological Organization of White Matter Network in Angelman Syndrome
Wei L, Du X, Yang Z, Ding M, Yang B, Wang J, Long S, Qiao Z, Jiang Y, Wang Y, Wang H. Disrupted Topological Organization of White Matter Network in Angelman Syndrome. Journal Of Magnetic Resonance Imaging 2022, 57: 1212-1221. PMID: 35856797, DOI: 10.1002/jmri.28360.Peer-Reviewed Original ResearchMeSH KeywordsAngelman SyndromeBrainChildChild, PreschoolDiffusion Tensor ImagingFemaleHumansMaleProspective StudiesWhite Matter
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
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
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
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
2008
Genomic analysis of the chromosome 15q11-q13 Prader-Willi syndrome region and characterization of transcripts for GOLGA8E and WHCD1L1 from the proximal breakpoint region
Jiang YH, Wauki K, Liu Q, Bressler J, Pan Y, Kashork CD, Shaffer LG, Beaudet AL. Genomic analysis of the chromosome 15q11-q13 Prader-Willi syndrome region and characterization of transcripts for GOLGA8E and WHCD1L1 from the proximal breakpoint region. BMC Genomics 2008, 9: 50. PMID: 18226259, PMCID: PMC2268926, DOI: 10.1186/1471-2164-9-50.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAngelman SyndromeAnimalsAutoantigensChromosome BreakageChromosome DeletionChromosomes, Human, Pair 15Conserved SequenceContig MappingCpG IslandsDNA MethylationElectrophoresis, Gel, Pulsed-FieldExonsGenomic ImprintingGenomicsHumansIntronsMiceOpen Reading FramesPrader-Willi SyndromeRNA, MessengerTranscription, GeneticWiskott-Aldrich Syndrome Protein FamilyConceptsLow-copy repeatsHuman genomeAllele-specific expression patternsProtein-coding genesHuman genome sequenceComplex chromosomal regionsCoiled-coil proteinsUCSC Genome BrowserCharacterization of transcriptsPolymorphic regionSequence-based physical mapProximal breakpoint regionCultured human cellsExtensive sequence analysisCopy number variationsGenomic orientationGene organizationNovel genesCentromeric deletion breakpointGenome sequenceSubfamily proteinsGenome browserGenomic analysisPhysical mapExact protein
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
2004
Human disorders of ubiquitination and proteasomal degradation
Jiang YH, Beaudet AL. Human disorders of ubiquitination and proteasomal degradation. Current Opinion In Pediatrics 2004, 16: 419-426. PMID: 15273504, DOI: 10.1097/01.mop.0000133634.79661.cd.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAngelman SyndromeAnimalsFanconi AnemiaGenetic Diseases, InbornGenetic Predisposition to DiseaseHumansNF-kappa BPolyendocrinopathies, AutoimmuneProteasome Endopeptidase ComplexUbiquitin-Activating EnzymesUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesUbiquitinsVon Hippel-Lindau DiseaseConceptsProteasomal degradationProteasomal subunitsAdditional functional classesUbiquitin E3 ligaseAutosomal recessive juvenile Parkinson's diseaseUbiquitin signalingE3 ligasesUbiquitin pathwayGenetic inborn errorsUbiquitin genesE3 ligaseSubcellular localizationUbiquitinationRelated proteinsMultiple functional defectsRelevant genesHuman disordersCongenital polycythemiaRegulatory signalingFanconi anemiaGenetic classesOvarian cancer susceptibilityFunctional classificationProteolytic degradationUbiquitin
2003
Disruption of the genomic imprint in trans with homologous recombination at Snrpn in ES cells
Tsai T, Bressler J, Jiang Y, Beaudet AL. Disruption of the genomic imprint in trans with homologous recombination at Snrpn in ES cells. Genesis 2003, 37: 151-161. PMID: 14666508, DOI: 10.1002/gene.10237.Peer-Reviewed Original ResearchConceptsPaternal alleleImprinting centerMaternal alleleSomatic mammalian cellsTrans-acting factorsActivation of expressionSNURF-SNRPN geneMouse ES cellsChromatin domainsGenomic imprintsImprinted domainMammalian cellsHomologous recombinationGene targetingHomologous associationES cellsComplete demethylationSNURF-SNRPNPrader-Willi syndromeExon 2AllelesGenesRecombinantsCellsDomainDerangements 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
1999
Genetics of Angelman Syndrome
Jiang Y, Lev-Lehman E, Bressler J, Tsai T, Beaudet A. Genetics of Angelman Syndrome. American Journal Of Human Genetics 1999, 65: 1-6. PMID: 10364509, PMCID: PMC1378067, DOI: 10.1086/302473.Peer-Reviewed Original Research
1998
Imprinting in Angelman and Prader-Willi syndromes
Jiang Y, Tsai T, Bressler J, Beaudet A. Imprinting in Angelman and Prader-Willi syndromes. Current Opinion In Genetics & Development 1998, 8: 334-342. PMID: 9691003, DOI: 10.1016/s0959-437x(98)80091-9.Peer-Reviewed Original ResearchMeSH KeywordsAngelman SyndromeAnimalsChromosomes, Human, Pair 15Genomic ImprintingHumansLigasesPrader-Willi SyndromeUbiquitin-Protein LigasesConceptsE6-AP ubiquitin-protein ligaseUbiquitin-protein ligaseAnalysis of methylationTissue-specific imprintingAngelman syndromeSNRPN promoterPrader-Willi syndromeAS genesMaternal chromosomesGene expressionGenomic sequencingPoint mutationsGenesBisulfite methodMethylationCandidate regionsImprintingHippocampal neuronsDrosophilaNecdinSNRPNLigaseChromosomesPromoterPurkinje cells
1997
The E6–AP Ubiquitin–Protein Ligase (UBE3A) Gene Is Localized within a Narrowed Angelman Syndrome Critical Region
Sutcliffe J, Jiang Y, Galjaard R, Matsuura T, Fang P, Kubota T, Christian S, Bressler J, Cattanach B, Ledbetter D, Beaudet A. The E6–AP Ubiquitin–Protein Ligase (UBE3A) Gene Is Localized within a Narrowed Angelman Syndrome Critical Region. Genome Research 1997, 7: 368-377. PMID: 9110176, PMCID: PMC139148, DOI: 10.1101/gr.7.4.368.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAngelman SyndromeAnimalsBlotting, NorthernBlotting, SouthernChromosome AberrationsChromosome MappingChromosomes, Artificial, YeastChromosomes, Human, Pair 15Cloning, MolecularCosmidsElectrophoresis, Gel, Pulsed-FieldFemaleGene DeletionGene DosageGene Expression Regulation, DevelopmentalGenetic MarkersGenomic ImprintingHumansIn Situ HybridizationLigasesMaleMiceMice, Mutant StrainsMolecular Sequence DataPaternityPrader-Willi SyndromeSequence Homology, Amino AcidSequence Homology, Nucleic AcidTissue DistributionTranscription, GeneticTranslocation, GeneticUbiquitin-Protein LigasesConceptsLigase geneUbiquitin protein ligase geneAngelman syndromeEntire transcriptional unitCandidate regionsMaternal-specific expressionE6-AP ubiquitinTranscriptional unitsPaternal deficiencyRT-PCR analysisMouse homologPrader-Willi syndromePaternal uniparental disomyPhysical mapDe novo truncating mutationsNovo truncating mutationsRecent identificationUBE3A locusMouse tissuesGenesUbe3a expressionLociUniparental disomyProtein levelsAS regionDe novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome
Matsuura T, Sutcliffe J, Fang P, Galjaard R, Jiang Y, Benton C, Rommens J, Beaudet A. De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nature Genetics 1997, 15: 74-77. PMID: 8988172, DOI: 10.1038/ng0197-74.Peer-Reviewed Original ResearchConceptsGene productsAngelman syndromeNovo truncating mutationsUbiquitin protein ligase geneUbiquitin-dependent proteolytic pathwayE6-AP ubiquitin-protein ligaseHuman genetic disordersUbiquitin-protein ligaseUBE3A geneTruncating mutationsEvidence of expressionUnlikely candidate geneGenetic disordersLigase geneParental allelesAS genesHuman chromosomesPaternal uniparental disomyCandidate genesDe novo truncating mutationsProteolytic pathwayNovo nonsense mutationGenesIntragenic mutationsMolecular defects