Exon 1 Disruption Alters Tissue-Specific Expression of Mouse p53 and Results in Selective Development of B Cell Lymphomas 英文参考文献.docVIP
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Exon 1 Disruption Alters Tissue-Specific Expression of Mouse p53 and Results in Selective Development of B Cell Lymphomas 英文参考文献
Exon1DisruptionAltersTissue-SpecificExpressionof
Mousep53andResultsinSelectiveDevelopmentofB
CellLymphomas
Y.JeffreyChiang1*¤,MichaelJ.Difilippantonio2,LinoTessarollo3,HerbertC.Morse4,RichardJ.Hodes1,5
1ExperimentalImmunologyBranch,NationalCancerInstitute,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica,2GeneticsBranch,Centerfor
Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 3Center for Cancer Research, Mouse Cancer
GeneticsProgram,NationalCancerInstitute,Frederick,Maryland,UnitedStatesofAmerica,4LaboratoryofImmunogenetics,NationalInstituteofAllergyandInfectious
Diseases, National Institutes of Health, Rockville, Maryland, United States of America, 5National Institute on Aging, National Institutes of Health, Bethesda, Maryland,
UnitedStatesofAmerica
Abstract
p53isatumorsuppressorgenemutatedin.50%ofhumancancers,whilep53deficiencyinmiceresultsincancersand
acceleratedmortality.ThymicTcelllymphomaisthemostcommonmalignancyinp53-deficientmice,makingitdifficultto
studytheroleofp53inothermalignancies.Toovercomethislimitation,weattemptedtogeneratemicewithareversible
p53knockout(p53rev/rev)byinsertingafloxedtranscriptionalstopintothefirstexonofp53,anticipatingthatthiswould
allowtissue-specificCre-mediatedexpressionofp53.Contrarytoexpectations,functionalp53proteinwasexpressedinthe
thymusandmultipleothertissuesofp53rev/revmiceintheabsenceofCre,whereasBcellsexpressedp53proteinonlyinthe
presenceofBcell-specificCD19-Cre.IntheabsenceofCre,76%ofp53rev/rev micedevelopedsplenicmarginalzoneBcell
lymphomas,indicatingsensitivityofthisBcellsubsettotransformationcausedbyp53deficiency.59-RACEidentifiedp53
mRNAtranscribedfromanovelstartsiteutilizedinthymocytesbutnotnormalBcellsorBcelllymphomasfromp53rev/rev
mice. The p53rev/rev mouse thus demonstrates an effect of p53 deficiency in development of splenic marginal zone
lymphomasandprovidesamodelforstudyofp53-deficienthumanBcelllymphomas.
Citati
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