Absence of Colony Stimulation Factor-1 Receptor Results in Loss of Microglia, Disrupted Brain Development and Olfactory Deficits 英文参考文献.docVIP

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Absence of Colony Stimulation Factor-1 Receptor Results in Loss of Microglia, Disrupted Brain Development and Olfactory Deficits 英文参考文献.doc

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Absence of Colony Stimulation Factor-1 Receptor Results in Loss of Microglia, Disrupted Brain Development and Olfactory Deficits 英文参考文献

AbsenceofColonyStimulationFactor-1ReceptorResults inLossofMicroglia,DisruptedBrainDevelopmentand OlfactoryDeficits BrynaErblich1.,LiyinZhu1.,AnneM.Etgen2,3,KostantinDobrenis2,JeffreyW.Pollard1,3* 1Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, New York, United States of America, 2Dominick Purpura DepartmentofNeuroscience,AlbertEinsteinCollegeofMedicine,NewYork,NewYork,UnitedStatesofAmerica, 3CenterfortheStudyofReproductiveBiologyand Women’sHealth,AlbertEinsteinCollegeofMedicine,NewYork,NewYork,UnitedStatesofAmerica Abstract Thebraincontainsnumerousmononuclearphagocytescalledmicroglia.Thesecellsexpressthetransmembranetyrosine kinasereceptorforthemacrophagegrowthfactorcolonystimulatingfactor-1(CSF-1R).UsingaCSF-1R-GFPreportermouse straincombinedwithlineagedefiningantibodystainingweshowinthepostnatalmousebrainthatCSF-1Risexpressed onlyinmicrogliaandnotneurons,astrocytesorglialcells.TostudyCSF-1Rfunctionweusedmicehomozygousforanull mutationintheCsflrgene.Inthesemicemicrogliaare.99%depletedatembryonicday16andday1post-partumbrain.At three weeks of age this microglial depletion continues in most regions of the brain although some contain clusters of roundedmicroglia.Despitethelossofmicroglia,embryonicbraindevelopmentappearsnormalbutduringthepost-natal period the brain architecture becomes perturbed with enlarged ventricles and regionally compressed parenchyma, phenotypesmostprominentintheolfactorybulbandcortex.Inthecortexthereisincreasedneuronaldensity,elevated numbersofastrocytesbutreducednumbersofoligodendrocytes.Csf1rnullsrarelysurvivetoadulthoodandthereforeto studytheroleofCSF-1RinolfactionweusedtheviablenullmutantsintheCsf1(Csf1op)genethatencodesoneofthetwo knownCSF-1Rligands.Food-findingexperimentsindicatethatolfactorycapacityissignificantlyimpairedintheabsenceof CSF-1. CSF-1R is therefore required for the development of microglia, for a fully functional olfactory system and the maintenanceofnormalbrainstru