2020
Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity
Xu J, Liu RJ, Fahey S, Frick L, Leckman J, Vaccarino F, Duman RS, Williams K, Swedo S, Pittenger C. Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity. American Journal Of Psychiatry 2020, 178: 48-64. PMID: 32539528, PMCID: PMC8573771, DOI: 10.1176/appi.ajp.2020.19070698.Peer-Reviewed Original ResearchConceptsStriatal cholinergic interneuronsCholinergic interneuronsMouse brain slicesObsessive-compulsive disorderControl subjectsBrain slicesPediatric autoimmune neuropsychiatric disordersIntravenous immunoglobulin treatmentAutoimmune neuropsychiatric disordersAcute mouse brain slicesParvalbumin-expressing GABAergic interneuronsPediatric obsessive-compulsive disorderBrain antigensImmunoglobulin treatmentBaseline serumStreptococcal infectionCritical cellular targetsSymptom improvementGABAergic interneuronsInduced autoimmunityIgG antibodiesMouse slicesIndependent cohortBehavioral pathologyNeuron types
2018
Chapter 49 Genetic susceptibility in obsessive-compulsive disorder
Fernandez TV, Leckman JF, Pittenger C. Chapter 49 Genetic susceptibility in obsessive-compulsive disorder. Handbook Of Clinical Neurology 2018, 148: 767-781. PMID: 29478613, DOI: 10.1016/b978-0-444-64076-5.00049-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsObsessive-compulsive disorderPotential novel therapeutic avenuesNovel therapeutic avenuesSpecific risk allelesUnderlying pathophysiologyLarge cohortLifelong disabilityImmune pathwaysTherapeutic avenuesNew treatmentsGenetic susceptibilityRisk allelesCandidate gene association studiesMouse knockout modelsGenetic findingsGene association studiesKnockout modelsOCD pathologyRisk variantsNotable inroadsGenetic variantsDisordersVulnerable pathwaysSubstantial genetic contributionRepetitive behaviors
2017
Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum
Frick L, Rapanelli M, Jindachomthong K, Grant P, Leckman JF, Swedo S, Williams K, Pittenger C. Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum. Brain Behavior And Immunity 2017, 69: 304-311. PMID: 29233751, PMCID: PMC5857467, DOI: 10.1016/j.bbi.2017.12.004.Peer-Reviewed Original ResearchConceptsGroup A beta-hemolytic streptococciCholinergic interneuronsPediatric Autoimmune Neuropsychiatric Disorder AssociatedNeuropsychiatric Disorder AssociatedStriatal cholinergic interneuronsStriatum of miceBeta-hemolytic streptococciBrain antigensPANDAS patientsIntravenous immunoglobulinStriatal interneuronsNeuropsychiatric symptomsObsessive-compulsive disorderSymptom improvementGABAergic interneuronsClinical trialsHealthy controlsDisorders AssociatedTic disordersChildhood onsetInterneuronsLocus of pathologyElevated bindingAntibodiesStriatum
2013
Brain Human Monoclonal Autoantibody from Sydenham Chorea Targets Dopaminergic Neurons in Transgenic Mice and Signals Dopamine D2 Receptor: Implications in Human Disease
Cox CJ, Sharma M, Leckman JF, Zuccolo J, Zuccolo A, Kovoor A, Swedo SE, Cunningham MW. Brain Human Monoclonal Autoantibody from Sydenham Chorea Targets Dopaminergic Neurons in Transgenic Mice and Signals Dopamine D2 Receptor: Implications in Human Disease. The Journal Of Immunology 2013, 191: 5524-5541. PMID: 24184556, PMCID: PMC3848617, DOI: 10.4049/jimmunol.1102592.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, BacterialAutoantibodiesBasal GangliaChildChoreaCross ReactionsDopamineDopaminergic NeuronsG(M1) GangliosideHEK293 CellsHumansImmunoglobulin GMiceMice, Inbred C57BLMice, TransgenicReceptors, Dopamine D2Recombinant Fusion ProteinsRheumatic FeverSignal TransductionStreptococcal InfectionsTransgenesConceptsSydenham's choreaDopamine D2 receptorsDopaminergic neuronsD2 receptorsTransgenic micePediatric autoimmune neuropsychiatric disordersDose-dependent inhibitoryMain neurologic manifestationsAutoimmune neuropsychiatric disordersBehavioral disordersHuman monoclonal autoantibodiesBrain AgsNeurologic manifestationsRheumatic feverChoreiform movementsTg miceBasal gangliaHuman dopamine D2 receptorAb reactivityTyrosine hydroxylaseAutoantibodiesB cellsMonoclonal autoantibodiesNeuropsychiatric disordersD2R
2006
Identification of pyruvate kinase as an antigen associated with Tourette syndrome
Kansy JW, Katsovich L, McIver KS, Pick J, Zabriskie JB, Lombroso PJ, Leckman JF, Bibb JA. Identification of pyruvate kinase as an antigen associated with Tourette syndrome. Journal Of Neuroimmunology 2006, 181: 165-176. PMID: 17011640, PMCID: PMC1853370, DOI: 10.1016/j.jneuroim.2006.08.007.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAmino Acid SequenceAnimalsAntibodies, BacterialAntigensAutoantibodiesBrainChildCross ReactionsHumansImmunohistochemistryLongitudinal StudiesMaleMiceMice, Inbred C57BLMolecular Sequence DataProspective StudiesPyruvate KinaseRatsSeroepidemiologic StudiesStreptococcal InfectionsTicsTourette SyndromeConceptsStreptococcal infectionObsessive-compulsive disorderTourette syndromeAutoimmune targetExacerbated symptomsBeta-hemolytic streptococcal infectionEarly-onset obsessive-compulsive disorderStreptococcal M proteinPediatric populationTic disordersImmune responseSurface antigenInfectious strainsSyndromeInfectionDisordersPyruvate kinaseM proteinPatientsImmunoreactivitySymptomsAntigenAntibodiesGlycolytic enzymesM1 isoform
2005
Sequence Variants in SLITRK1 Are Associated with Tourette's Syndrome
Abelson JF, Kwan KY, O'Roak BJ, Baek DY, Stillman AA, Morgan TM, Mathews CA, Pauls DL, Rašin M, Gunel M, Davis NR, Ercan-Sencicek AG, Guez DH, Spertus JA, Leckman JF, Dure LS, Kurlan R, Singer HS, Gilbert DL, Farhi A, Louvi A, Lifton RP, Šestan N, State MW. Sequence Variants in SLITRK1 Are Associated with Tourette's Syndrome. Science 2005, 310: 317-320. PMID: 16224024, DOI: 10.1126/science.1116502.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdolescentAnimalsAttention Deficit Disorder with HyperactivityBrainChildChild, PreschoolChromosome InversionChromosome MappingChromosomes, Human, Pair 13DNADNA Mutational AnalysisFemaleFrameshift MutationHumansIn Situ Hybridization, FluorescenceMaleMembrane ProteinsMiceMutationNerve Tissue ProteinsPedigreeSequence Analysis, DNATourette SyndromeConceptsSequence variantsTourette syndromeChromosomal inversionsFrameshift mutantsCandidate genesExpression patternsControl chromosomesPrimary neuronal culturesFrameshift mutationSLITRK1Independent occurrenceMotor ticsDevelopmental neuropsychiatric disordersChronic vocalNeuronal culturesIdentical variantsUnrelated probandsBrain regionsNeuropsychiatric disordersSyndrome
2003
Expression of BEN, a member of TFII-I family of transcription factors, during mouse pre- and postimplantation development
Bayarsaihan D, Bitchevaia N, Enkhmandakh B, Tussie-Luna MI, Leckman JF, Roy A, Ruddle F. Expression of BEN, a member of TFII-I family of transcription factors, during mouse pre- and postimplantation development. Gene Expression Patterns 2003, 3: 579-589. PMID: 12971990, DOI: 10.1016/s1567-133x(03)00118-2.Peer-Reviewed Original ResearchConceptsTFII-I familyTranscription factorsPostimplantation developmentEarly gastrulation stagesExtensive expression patternMouse preTwo-cell stageGastrulation stageEarly blastocyst stageRepeat domainNuclear localizationExpression patternsTissue developmentBlastocyst stageMost tissuesCytoplasmExpressionExtensive expressionHomez, a homeobox leucine zipper gene specific to the vertebrate lineage
Bayarsaihan D, Enkhmandakh B, Makeyev A, Greally JM, Leckman JF, Ruddle FH. Homez, a homeobox leucine zipper gene specific to the vertebrate lineage. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 10358-10363. PMID: 12925734, PMCID: PMC193566, DOI: 10.1073/pnas.1834010100.Peer-Reviewed Original ResearchConceptsLeucine zipper-like motifHomeobox-containing proteinLobe-finned fishesVertebrate homeobox genesFamily of genesLeucine zipper genesUnusual structural organizationZipper-like motifOverall protein structureVertebrate lineageComplementation modelZipper genePufferfish homologsHomeodomain sequencesMammalian sequencesMouse geneZHX familyMouse developmentAcidic domainHomeobox genesPhylogenetic analysisHomeodomain factorsGenomic analysisAtypical homeodomainHomez
2002
Maternal behavior and developmental psychopathology
Leckman JF, Herman AE. Maternal behavior and developmental psychopathology. Biological Psychiatry 2002, 51: 27-43. PMID: 11801229, DOI: 10.1016/s0006-3223(01)01277-x.Peer-Reviewed Original ResearchConceptsMaternal behaviorNeuronal nitric oxide synthaseEstrogen alpha receptorsNitric oxide synthaseMouse strain backgroundDopamine beta hydroxylaseGene knockout dataAnimal model systemsGene knockout studiesGene knockout technologyPeer-reviewed journalsOxide synthaseAlpha receptorsBehavioral deficitsSearch of literatureBeta hydroxylaseDisease pathogenesisTranscription factorsMolecular basisGenetic factorsKnockout studiesSpecific genesKnockout dataKnockout technologyStrain background
1991
Detection of homeobox genes in development and evolution.
Murtha MT, Leckman JF, Ruddle FH. Detection of homeobox genes in development and evolution. Proceedings Of The National Academy Of Sciences Of The United States Of America 1991, 88: 10711-10715. PMID: 1720547, PMCID: PMC53000, DOI: 10.1073/pnas.88.23.10711.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBiological EvolutionCiona intestinalisCodonDipteraDrosophilaEmbryo, MammalianEmbryo, NonmammalianGenes, HomeoboxMaleMiceMolecular Sequence DataOligodeoxyribonucleotidesPolymerase Chain ReactionRestriction MappingRNASequence Homology, Nucleic AcidTelencephalonConceptsHomeobox genesHomeobox sequencesDNA-binding regulatory proteinsDiverse metazoan speciesSurvey of sequencesMouse genomic DNAImportant model systemPopulations of DNAMetazoan speciesAncient roleMetazoan evolutionPolymerase chain reactionGenomic organizationDrosophila H2.0Regulatory proteinsHlx geneGenomic DNAStudy of developmentMouse telencephalonNovel sequencesGenesOligonucleotide primersHomeodomainModel systemRNA