Cell-Extrinsic Defective Lymphocyte Development in Lmna-- Mice 英文参考文献.docVIP

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Cell-Extrinsic Defective Lymphocyte Development in Lmna-- Mice 英文参考文献.doc

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Cell-Extrinsic Defective Lymphocyte Development in Lmna-- Mice 英文参考文献

Cell-ExtrinsicDefectiveLymphocyteDevelopmentin Lmna-/- Mice J.ScottHale1.,RichardL.Frock2.,SaraA.Mamman2,PamelaJ.Fink1.,BrianK.Kennedy2*. 1DepartmentofImmunology,UniversityofWashington,Seattle,Washington,UnitedStatesofAmerica,2DepartmentofBiochemistry,UniversityofWashington,Seattle, Washington,UnitedStatesofAmerica Abstract Background:MutationsintheLMNAgene,whichencodesallA-typelamins,resultinavarietyofhumandiseasestermed laminopathies.Lmna-/- miceappearnormalatbirthbutbecomeruntedasearlyas2weeksofageanddevelopmultiple tissuedefectsthatmimicsomeaspectsofhumanlaminopathies.Lmna-/-micealsodisplaysmallerspleensandthymuses.In this study, we investigated whether altered lymphoid organ sizes are correlated with specific defects in lymphocyte development. PrincipalFindings:Lmna-/-micedisplayedsevereage-dependentdefectsinTandBcelldevelopmentwhichcoincidedwith runting. Lmna-/- bone marrow reconstituted normal T and B cell development in irradiated wild-type recipients, driving + + generationoffunctionalandself-MHCrestrictedCD4 andCD8 Tcells.TransplantationofLmna-/-neonatalthymuslobes intosyngeneicwild-typerecipientsresultedingoodengraftmentofthymictissueandnormalthymocytedevelopment. Conclusions: Collectively, these data demonstrate that the severe defects in lymphocyte development that characterize Lmna-/- mice donotresultdirectlyfromthelossofA-typelaminfunctioninlymphocytesorthymicstroma.Instead,the immunedefectsinLmna-/-micelikelyreflectindirectdamage,perhapsresultingfromprolongedstressduetothestriated muscledystrophiesthatoccurinthesemice. Citation:HaleJS,FrockRL,MammanSA,FinkPJ,KennedyBK(2010)Cell-ExtrinsicDefectiveLymphocyteDevelopmentinLmna-/-Mice.PLoSONE5(4):e10127. doi:10.1371/journal.pone.0010127 Editor:DeryaUnutmaz,NewYorkUniversity,UnitedStatesofAmerica ReceivedJanuary8,2010;AcceptedFebruary23,2010;PublishedApril12,2010 Copyright:?2010Haleetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted u