2024
Massively parallel disruption of enhancers active in human neural stem cells
Geller E, Noble M, Morales M, Gockley J, Emera D, Uebbing S, Cotney J, Noonan J. Massively parallel disruption of enhancers active in human neural stem cells. Cell Reports 2024, 43: 113693. PMID: 38271204, PMCID: PMC11078116, DOI: 10.1016/j.celrep.2024.113693.Peer-Reviewed Original ResearchHuman neural stem cellsNeural stem cellsStem cellsProliferation phenotypeAssociated with neurodevelopmental disordersNeurodevelopmental disordersEnhanced disruptionHuman Accelerated RegionsNeural progenitor proliferationEffects of genetic variationHuman cortical evolutionProgenitor proliferationSelf-RenewalNeural progenitorsProgenitor populationsCerebral cortexChromatin interactionsHuman cerebral cortexNeural progenitor populationsGene regulationRegulatory elementsConserved regionGene disruptionGenetic variationRegulatory relationships
2021
Cas9-expressing chickens and pigs as resources for genome editing in livestock
Rieblinger B, Sid H, Duda D, Bozoglu T, Klinger R, Schlickenrieder A, Lengyel K, Flisikowski K, Flisikowska T, Simm N, Grodziecki A, Perleberg C, Bähr A, Carrier L, Kurome M, Zakhartchenko V, Kessler B, Wolf E, Kettler L, Luksch H, Hagag I, Wise D, Kaufman J, Kaufer B, Kupatt C, Schnieke A, Schusser B. Cas9-expressing chickens and pigs as resources for genome editing in livestock. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2022562118. PMID: 33658378, PMCID: PMC7958376, DOI: 10.1073/pnas.2022562118.Peer-Reviewed Original ResearchConceptsCross-species comparisonsGenome editingMolecular basis of healthFunction of Cas9Phylogenetically distant speciesTargeted gene disruptionGeneration of transgenic chickensIn vivo genome editingDistant speciesReverse geneticsDNA fragmentationGene disruptionGenetic methodsTarget genesMolecular basisCRISPR-Cas9Transgenic chickensCas9Cell typesSpeciesTranslational biomedical researchGeneticsChickenBases of healthPigs
2018
Recent advances of animal model of focal segmental glomerulosclerosis
Yang J, Dettmar A, Kronbichler A, Gee H, Saleem M, Kim S, Shin J. Recent advances of animal model of focal segmental glomerulosclerosis. Clinical And Experimental Nephrology 2018, 22: 752-763. PMID: 29556761, DOI: 10.1007/s10157-018-1552-8.Peer-Reviewed Original ResearchConceptsAnimal models of focal segmental glomerulosclerosisFocal segmental glomerulosclerosisGroups of animal modelsModel of focal segmental glomerulosclerosisAnimal modelsSegmental glomerulosclerosisCD2-associated proteinCombination of genetic mutationsPathophysiology of focal segmental glomerulosclerosisGenetic engineering techniquesStudy focal segmental glomerulosclerosisGene disruptionGenetic basisGenetic animal modelsHuman diseasesTRPC6 channelsRenal ablationPodocyte toxinGenetic mutationsComplex pathophysiologyMouse backgroundSlit diaphragmDiphtheria toxinPodocyte injuryAdaptive responseA CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies
Breslow DK, Hoogendoorn S, Kopp AR, Morgens DW, Vu BK, Kennedy MC, Han K, Li A, Hess GT, Bassik MC, Chen JK, Nachury MV. A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies. Nature Genetics 2018, 50: 460-471. PMID: 29459677, PMCID: PMC5862771, DOI: 10.1038/s41588-018-0054-7.Peer-Reviewed Original ResearchConceptsFunctional genomic screensGenome-wide CRISPRCiliary functionHedgehog-responsive cellsCiliary signalingΕ-tubulinProtein complexesGenomic screenEmbryonic developmentGene disruptionPrimary ciliaΔ-tubulinNovel componentCiliopathiesCRISPRCiliary structureUnbiased toolHedgehogUnifying causeScreenGenesSignalingCiliaSystematic analysisPathway
2014
The Major Cellular Sterol Regulatory Pathway Is Required for Andes Virus Infection
Petersen J, Drake MJ, Bruce EA, Riblett AM, Didigu CA, Wilen CB, Malani N, Male F, Lee FH, Bushman FD, Cherry S, Doms RW, Bates P, Briley K. The Major Cellular Sterol Regulatory Pathway Is Required for Andes Virus Infection. PLOS Pathogens 2014, 10: e1003911. PMID: 24516383, PMCID: PMC3916400, DOI: 10.1371/journal.ppat.1003911.Peer-Reviewed Original ResearchConceptsRegulatory pathwaysHuman haploid cellsParallel genetic screensGenetic screenPathogenic New World hantavirusesGenomic screenAndes virusHaploid cellsGene disruptionRNA interferenceANDV entryDeficient cellsCellular requirementsCellular cholesterolRNA virusesANDV infectionLarge familyPharmacologic inhibitionWorldwide distributionAndes Virus InfectionNew World hantavirusesVirus bindingPathwayHost factorsSterol synthesis
2011
Mapping copy number variation by population-scale genome sequencing
Mills RE, Walter K, Stewart C, Handsaker RE, Chen K, Alkan C, Abyzov A, Yoon SC, Ye K, Cheetham RK, Chinwalla A, Conrad DF, Fu Y, Grubert F, Hajirasouliha I, Hormozdiari F, Iakoucheva LM, Iqbal Z, Kang S, Kidd JM, Konkel MK, Korn J, Khurana E, Kural D, Lam HY, Leng J, Li R, Li Y, Lin CY, Luo R, Mu XJ, Nemesh J, Peckham HE, Rausch T, Scally A, Shi X, Stromberg MP, Stütz AM, Urban AE, Walker JA, Wu J, Zhang Y, Zhang ZD, Batzer MA, Ding L, Marth GT, McVean G, Sebat J, Snyder M, Wang J, Ye K, Eichler EE, Gerstein MB, Hurles ME, Lee C, McCarroll SA, Korbel JO. Mapping copy number variation by population-scale genome sequencing. Nature 2011, 470: 59-65. PMID: 21293372, PMCID: PMC3077050, DOI: 10.1038/nature09708.Peer-Reviewed Original ResearchConceptsMost structural variantsStructural variantsSequencing-based association studiesUnbalanced structural variantsGenomic structural variantsFunctional impactDNA sequencing dataSV hotspotsSV discoveryHuman genomeNucleotide resolutionGene disruptionAdditional structural variantsHigh-frequency deletionSequencing dataGenome sequencingAssociation studiesTandem duplicationNumber variationsGene deletionPartial gene deletionsDeletionCommon mechanismForm of variationSize spectra
2010
Targeted deletion of βIII spectrin impairs synaptogenesis and generates ataxic and seizure phenotypes
Stankewich MC, Gwynn B, Ardito T, Ji L, Kim J, Robledo RF, Lux SE, Peters LL, Morrow JS. Targeted deletion of βIII spectrin impairs synaptogenesis and generates ataxic and seizure phenotypes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 6022-6027. PMID: 20231455, PMCID: PMC2851889, DOI: 10.1073/pnas.1001522107.Peer-Reviewed Original ResearchConceptsBetaIII spectrinSpinocerebellar ataxia type 5Spectrin membrane skeletonTargeted gene disruptionAmino acid transportersExcitatory amino acid transportersImpairs synaptogenesisProtein traffickingSeizure disorderGene disruptionDark Purkinje cellsMembrane skeletonAlphaII-spectrinAcid transportersMechanistic basisPurkinje cellsMembrane channelsGlutamate receptor deltaIntracellular pathwaysSpectrin bindsSynaptic proteinsSpectrinReceptor deltaProteinGolgi profiles
2008
Genome-Wide Transposon Mutagenesis in Pathogenic Leptospira Species
Murray GL, Morel V, Cerqueira GM, Croda J, Srikram A, Henry R, Ko AI, Dellagostin OA, Bulach DM, Sermswan RW, Adler B, Picardeau M. Genome-Wide Transposon Mutagenesis in Pathogenic Leptospira Species. Infection And Immunity 2008, 77: 810-816. PMID: 19047402, PMCID: PMC2632054, DOI: 10.1128/iai.01293-08.Peer-Reviewed Original ResearchConceptsTransposon mutagenesisTransposon mutantsGenome-wide transposon mutagenesisL. interrogansTransposon insertion sitesNovel virulence factorsEssential genesHypothetical genesGene functionGenome sequenceTransposon insertionGene disruptionGenetic manipulationDifferent genesGenetic analysisHeme biosynthesisPathogenic Leptospira speciesMutantsSequence analysisGenesVirulence factorsInsertional hot spotsLocation of insertionGenomeMutagenesis
2005
HPV16 E2 gene disruption and polymorphisms of E2 and LCR: Some significant associations with cervical cancer in Indian women
Bhattacharjee B, Sengupta S. HPV16 E2 gene disruption and polymorphisms of E2 and LCR: Some significant associations with cervical cancer in Indian women. Gynecologic Oncology 2005, 100: 372-378. PMID: 16246404, DOI: 10.1016/j.ygyno.2005.09.016.Peer-Reviewed Original ResearchConceptsE2 disruptionE2 geneE2 gene disruptionIntact E2 geneIndian womenBi-directional sequencingAsian-American variantsNucleotide sequence alterationsDNA-binding regionHPV16 E2 geneCaCx developmentHPV16 isolatesCompared to controlsChi-square testCaCx casesFisher's exactCervical cancerViral factorsHPV16Nucleotide variationsE subgroupGene disruptionSequence alterationsPCR amplificationNucleotide
2002
Transcription factor AP-2gamma is essential in the extra-embryonic lineages for early postimplantation development.
Auman HJ, Nottoli T, Lakiza O, Winger Q, Donaldson S, Williams T. Transcription factor AP-2gamma is essential in the extra-embryonic lineages for early postimplantation development. Development 2002, 129: 2733-47. PMID: 12015300, DOI: 10.1242/dev.129.11.2733.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlastocystBreast NeoplasmsDNA-Binding ProteinsEmbryo ImplantationEmbryonic and Fetal DevelopmentFemaleGene Expression Regulation, DevelopmentalGenotypeHumansMiceMice, KnockoutMorphogenesisPlacentaPolymerase Chain ReactionPregnancyRestriction MappingTranscription Factor AP-2Transcription FactorsConceptsExtra-embryonic lineagesAP-2gammaAnterior-posterior patterningStem cell maintenanceEarly postimplantation developmentExtra-embryonic tissuesAcid-responsive genesAP-2 familyRetinoic acid-responsive geneTrophoblast-specific expressionMaternal-embryonic interfaceMammalian developmentDays post coitumExtra-embryonic membranesCell maintenanceTranscription factorsEmbryonic developmentGene disruptionBiological functionsMouse embryosPostimplantation developmentPreimplantation embryosMutantsMolecular analysisNormal development
2001
In Vivo Effects of Uncoupling Protein-3 Gene Disruption on Mitochondrial Energy Metabolism*
Cline G, Vidal-Puig A, Dufour S, Cadman K, Lowell B, Shulman G. In Vivo Effects of Uncoupling Protein-3 Gene Disruption on Mitochondrial Energy Metabolism*. Journal Of Biological Chemistry 2001, 276: 20240-20244. PMID: 11274222, DOI: 10.1074/jbc.m102540200.Peer-Reviewed Original ResearchConceptsATP synthesisEnergy metabolismSkeletal muscleMitochondrial oxidative phosphorylationMitochondrial energy metabolismGene disruptionRatio of ATPOxidative phosphorylationATP productionTricarboxylic acid cycle fluxWhole-body levelUCP3KO miceWhole-body energy expenditureCellular levelProtein 3Cycle fluxLabeling experimentsFirst evidenceBody energy expenditureMetabolismVivoMeasurement of ratesPhosphorylationEnergy expenditureUCP3
2000
Increased Energy Expenditure, Decreased Adiposity, and Tissue-Specific Insulin Sensitivity in Protein-Tyrosine Phosphatase 1B-Deficient Mice
Klaman L, Boss O, Peroni O, Kim J, Martino J, Zabolotny J, Moghal N, Lubkin M, Kim Y, Sharpe A, Stricker-Krongrad A, Shulman G, Neel B, Kahn B. Increased Energy Expenditure, Decreased Adiposity, and Tissue-Specific Insulin Sensitivity in Protein-Tyrosine Phosphatase 1B-Deficient Mice. Molecular And Cellular Biology 2000, 20: 5479-5489. PMID: 10891488, PMCID: PMC85999, DOI: 10.1128/mcb.20.15.5479-5489.2000.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBody WeightCarrier ProteinsEnergy MetabolismFemaleGlucoseGlucose Tolerance TestHomeostasisHyperinsulinismInsulin ResistanceIon ChannelsLeptinMaleMembrane ProteinsMembrane Transport ProteinsMiceMice, Inbred C57BLMice, Mutant StrainsMitochondrial ProteinsMuscle, SkeletalProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine PhosphatasesProteinsRNA, MessengerUncoupling Protein 1Uncoupling Protein 2Uncoupling Protein 3ConceptsProtein tyrosine phosphatasePTP-1BMajor protein tyrosine phosphataseProtein tyrosine phosphatase 1BSignal transduction pathwaysTargeted gene disruptionInsulin-stimulated glucose uptakeGene disruptionTransduction pathwaysFat cell massPhosphatase 1BMajor regulatorProtein mRNA expressionCell massNull miceSkeletal muscleDeficient miceGlucose uptakeBasal metabolic rateInsulin actionMetabolic ratePhosphataseFat storesDiet-induced obesityAdipocyte number
1999
Large-scale analysis of the yeast genome by transposon tagging and gene disruption
Ross-Macdonald P, Coelho P, Roemer T, Agarwal S, Kumar A, Jansen R, Cheung K, Sheehan A, Symoniatis D, Umansky L, Heidtman M, Nelson F, Iwasaki H, Hager K, Gerstein M, Miller P, Roeder G, Snyder M. Large-scale analysis of the yeast genome by transposon tagging and gene disruption. Nature 1999, 402: 413-418. PMID: 10586881, DOI: 10.1038/46558.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsDNA Transposable ElementsEscherichia coliFungal ProteinsGene Expression ProfilingGenetic TechniquesGenome, FungalMolecular Sequence DataMutagenesisOligonucleotide Array Sequence AnalysisOpen Reading FramesPhenotypePolymerase Chain ReactionSaccharomyces cerevisiaeTransformation, GeneticConceptsGene functionDisruption phenotypesLarge-scale analysisNon-annotated open reading framesGenome-wide analysisOpen reading frameSingle genetic backgroundTransposon taggingYeast genomeYeast mutantsGenomic scaleYeast SaccharomycesDifferent growth conditionsProtein localizationGene disruptionReading frameGene expressionFunctional analysisVegetative growthGenetic backgroundGenesGenomeTransposonGrowth conditionsYeast
1998
Release of cell cycle constraints in mouse melanocytes by overexpressed mutant E2F1E132, but not by deletion of p16INK4A or p21WAF1/CIP1
Halaban R, Cheng E, Zhang Y, Mandigo C, Miglarese M. Release of cell cycle constraints in mouse melanocytes by overexpressed mutant E2F1E132, but not by deletion of p16INK4A or p21WAF1/CIP1. Oncogene 1998, 16: 2489-2501. PMID: 9627115, DOI: 10.1038/sj.onc.1201773.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell CycleCell Cycle ProteinsCell SurvivalCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p21CyclinsDNA-Binding ProteinsE2F Transcription FactorsE2F1 Transcription FactorGene Expression RegulationHumansMelanocytesMiceMice, NudeMutagenesisProtein BiosynthesisRecombinant Fusion ProteinsRetinoblastoma ProteinRetinoblastoma-Binding Protein 1Tetradecanoylphorbol AcetateTranscription Factor DP1Transcription FactorsConceptsP21WAF1/CIP1Cell cycle progressionMouse melanocytesTarget genesCycle progressionRetinoblastoma tumor suppressor proteinE2F-mediated transactivationCell cycle constraintsTumor suppressor proteinRole of E2F1Deletion of p16INK4AFree E2FExpression of RbGene disruptionSuppressor proteinEctopic expressionHallmark of melanomaTetradecanoyl phorbol 13Loss of p16INK4aConstitutive expressionMelanoma cell linesCell deathNormal melanocytesIndependent growthMelanocyte growth
1994
Large-scale analysis of gene expression, protein localization, and gene disruption in Saccharomyces cerevisiae.
Burns N, Grimwade B, Ross-Macdonald P, Choi E, Finberg K, Roeder G, Snyder M. Large-scale analysis of gene expression, protein localization, and gene disruption in Saccharomyces cerevisiae. Genes & Development 1994, 8: 1087-1105. PMID: 7926789, DOI: 10.1101/gad.8.9.1087.Peer-Reviewed Original ResearchConceptsFusion proteinFusion geneSubcellular locationGene productsCytoplasmic dotsVegetative growthVegetative cellsSpecific subcellular locationsSpindle pole bodyEncoded gene productsLarge-scale screenOpen reading frameGal fusion proteinLife cycleYeast genesYeast genomeGenomic libraryPole bodyHomozygous diploidsHaploid cellsProtein localizationIndirect immunofluorescence analysisGene disruptionReading frameDNA sequences
1992
SEC6 encodes an 85 kDa soluble protein required for exocytosis in yeast
Potenza M, Bowser R, Müller H, Novick P. SEC6 encodes an 85 kDa soluble protein required for exocytosis in yeast. Yeast 1992, 8: 549-558. PMID: 1523887, DOI: 10.1002/yea.320080706.Peer-Reviewed Original ResearchConceptsTemperature-sensitive growth defectPost-Golgi vesiclesSingle-copy geneOpen reading frameSaccharomyces cerevisiae cellsMarker rescue experimentsSec6 geneKnown proteinsSec mutantsCopy geneSec6-4Growth defectExtensive homologyGene disruptionReading frameNucleotide sequenceGene productsPlasma membraneSynthetic lethalityCerevisiae cellsSoluble proteinYeast lysateRescue experimentsAmino acidsSec6
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