2022
Modeling uniquely human gene regulatory function via targeted humanization of the mouse genome
Dutrow EV, Emera D, Yim K, Uebbing S, Kocher AA, Krenzer M, Nottoli T, Burkhardt DB, Krishnaswamy S, Louvi A, Noonan JP. Modeling uniquely human gene regulatory function via targeted humanization of the mouse genome. Nature Communications 2022, 13: 304. PMID: 35027568, PMCID: PMC8758698, DOI: 10.1038/s41467-021-27899-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCell DifferentiationChondrocytesChondrogenesisEmbryo, MammalianEnhancer Elements, GeneticEpigenesis, GeneticExtremitiesGene Expression ProfilingGene Expression RegulationGene Knock-In TechniquesGenomeHomeodomain ProteinsHomozygoteHumansMesodermMice, Inbred C57BLModels, GeneticPan troglodytesPromoter Regions, GeneticTime FactorsConceptsHuman Accelerated RegionsGene expressionHuman-specific sequence changesDevelopmental gene regulationSingle-cell RNA sequencingGene regulatory functionsHuman evolutionEndogenous gene expressionAlters gene expressionSkeletal patterningMolecular functionsGene regulationChondrogenic mesenchymeMouse genomeRegulatory modificationHomozygous embryosLimb developmentTranscriptional enhancersTranscription factorsRNA sequencingEnhancer activityMouse embryosRegulatory functionsAccelerated regionSequence changes
2021
Mouse Embryonic Fibroblasts Isolated From Nthl1 D227Y Knockin Mice Exhibit Defective DNA Repair and Increased Genome Instability
Marsden CG, Das L, Nottoli TP, Kathe SD, Doublié S, Wallace SS, Sweasy JB. Mouse Embryonic Fibroblasts Isolated From Nthl1 D227Y Knockin Mice Exhibit Defective DNA Repair and Increased Genome Instability. DNA Repair 2021, 109: 103247. PMID: 34826736, PMCID: PMC8787541, DOI: 10.1016/j.dnarep.2021.103247.Peer-Reviewed Original ResearchConceptsGenomic instabilityEmbryonic fibroblastsExogenous DNA damaging agentsBifunctional DNA glycosylaseIncreased genome instabilityGenome editing technologyMurine embryonic fibroblastsDNA damaging agentsMouse embryonic fibroblastsNormal cellular metabolismDefective DNA repairHomozygous stateDNA glycosylase 1Genome instabilityMutant MEFsReplication stressDNA repairCellular phenotypesDNA glycosylaseEditing technologyCellular metabolismDamaging agentsWT proteinOxidative DNA damagePyrimidine lesions
2012
Y265C DNA polymerase beta knockin mice survive past birth and accumulate base excision repair intermediate substrates
Senejani AG, Dalal S, Liu Y, Nottoli TP, McGrath JM, Clairmont CS, Sweasy JB. Y265C DNA polymerase beta knockin mice survive past birth and accumulate base excision repair intermediate substrates. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 6632-6637. PMID: 22493258, PMCID: PMC3340078, DOI: 10.1073/pnas.1200800109.Peer-Reviewed Original ResearchConceptsDNA polymerase activityWT littermatesKnockin miceMiceMouse embryo fibroblastsChromosomal aberrationsWT mouse embryo fibroblastsNormal Mendelian ratioSlow proliferationPolymerase activityBirthΒ variantCell deathEmbryo fibroblastsWT cellsExcision repair pathwayDNA repair systemsCellular metabolismBase excision repair pathwayFibroblastsHoursHigh levelsHomozygous mutantsKey players