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
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 ResearchConceptsSHANK 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
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