2016
Modeling altered T-cell development with induced pluripotent stem cells from patients with RAG1-dependent immune deficiencies
Brauer PM, Pessach IM, Clarke E, Rowe JH, Ott de Bruin L, Lee YN, Dominguez-Brauer C, Comeau AM, Awong G, Felgentreff K, Zhang YH, Bredemeyer A, Al-Herz W, Du L, Ververs F, Kennedy M, Giliani S, Keller G, Sleckman BP, Schatz DG, Bushman FD, Notarangelo LD, Zúñiga-Pflücker JC. Modeling altered T-cell development with induced pluripotent stem cells from patients with RAG1-dependent immune deficiencies. Blood 2016, 128: 783-793. PMID: 27301863, PMCID: PMC4982452, DOI: 10.1182/blood-2015-10-676304.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedDNA BreaksGenes, RAG-1Homeodomain ProteinsHumansInduced Pluripotent Stem CellsInfantMutationReceptors, Antigen, T-Cell, alpha-betaSevere Combined ImmunodeficiencyT-LymphocytesV(D)J RecombinationConceptsInduced pluripotent stem cellsT cell developmentPluripotent stem cellsT cell receptorStem cellsOmenn syndrome patientsSingle-strand DNA breaksHuman induced pluripotent stem cellsControl iPSCsDeep-sequencing analysisT lineage cellsHuman T-cell developmentT cell progenitorsIPSC-derived cellsJoining genesImpaired T-cell differentiationDNA breaksSame geneN-terminalImmune system developmentLocus rearrangementT cell differentiationPatient cellsRecombination activityGenetic defects
2009
Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation
Giblin W, Chatterji M, Westfield G, Masud T, Theisen B, Cheng HL, DeVido J, Alt FW, Ferguson DO, Schatz DG, Sekiguchi J. Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation. Blood 2009, 113: 2965-2975. PMID: 19126872, PMCID: PMC2662642, DOI: 10.1182/blood-2008-07-165167.Peer-Reviewed Original ResearchConceptsDouble-strand breaksHypomorphic RAG1 mutationsImmune system dysfunctionDNA rearrangementsKnockin mouse modelP53 mutant backgroundAberrant DNA rearrangementsDNA double-strand breaksPremature immunosenescenceDNA end processingSystem dysfunctionRecombination signal sequencesMouse modelRAG1 mutationsImmune systemMice exhibitAntigen receptor genesThymic lymphomasTumor developmentVivo evidenceMutant backgroundLymphocyte developmentSignal sequenceReceptor geneHypomorphic mutations
2003
Defective DNA Repair and Increased Genomic Instability in Artemis-deficient Murine Cells
Rooney S, Alt FW, Lombard D, Whitlow S, Eckersdorff M, Fleming J, Fugmann S, Ferguson DO, Schatz DG, Sekiguchi J. Defective DNA Repair and Increased Genomic Instability in Artemis-deficient Murine Cells. Journal Of Experimental Medicine 2003, 197: 553-565. PMID: 12615897, PMCID: PMC2193825, DOI: 10.1084/jem.20021891.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBleomycinCell LineChromosome AberrationsDNADNA DamageDNA RepairDNA-Binding ProteinsEmbryo, MammalianEndonucleasesGene TargetingGenomeHomeodomain ProteinsHumansIn Situ Hybridization, FluorescenceMiceMutationNuclear ProteinsRadiation, IonizingRecombination, GeneticSequence Analysis, DNASevere Combined ImmunodeficiencyStem CellsTelomere