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1、Chapter8AdiposeTissue-SpecificPPARgGeneTargetingWeiminHeAbstractThenuclearreceptorperoxisomeproliferatoractivatedreceptorgamma(PPARg)ismostabundantlyexpressedinadiposetissueandhasbeenshowntoplayimperativerolesincontrollingadipogenesisandlipogenesisinculturedcellsystems
2、invitroaswellasinmiceandhumans.However,itisunclearhowimportanttherolethisreceptorplaysinregulatingphysiologicalfunctionsofmatureadipocytesinvivo.TheCre-loxPgenetargetingstrategyisemployedtospeciÞcallydisruptPPARginmatureadipocytesinmice.Inthischapter,Iwilldescribegene
3、rationofÒßoxedÓPPARgmice,whichbearloxPsequencesintheintronsofPPARggenelocusßankingthecodingexons1and2ofPPARgandcreationoftheaP2-Cretransgenicmice,whichexpressCrerecombinaseunderthecontrolofthepromoterofadipocytefattyacidbindingprotein(aP2).Crossingofthetwomouselinesre
4、sultsindeletionofPPARggeneonlyindifferen-tiatedadipocytesinCrepositivemice.Keywords:Adiposetissue,PPARg,Genetargeting,Embryonicstemcells,loxP,Cretransgenicmice1.IntroductionAdiposetissuewasonceregardedasatissuethatonlystoreslipidsastriglyceridesinfeedingstatesandrelea
5、sesnonesteriÞedfattyacidsasenergysourcesforperipheraltissuesinfastingstates.Studiesinthelastseveraldecades,however,haveestablishedadi-posetissueasanimportantendocrineorgan/tissue(1).Thistissuesecretesmanyendocrinefactorscalledadipocytokines(oradipok-ines)andsomeproinß
6、ammatoryfactors(inobesecondition)tocriticallyregulatemanyimportantpathophysiologicalactivities,includingfoodintake(2),immunityandinßammation(3,4),sys-temicglucoseandlipidmetabolism(5),andbonehomeostasis(6),tonameafew.LackofsufÞcientamountoffunctionaladiposetissue(know
7、naslipodystrophy)isassociatedwithadversehealthMostafaZ.BadrandJihanYoussef(eds.),PeroxisomeProliferator-ActivatedReceptors(PPARs):MethodsandProtocols,MethodsinMolecularBiology,vol.952,DOI10.1007/978-1-62703-155-4_8,©SpringerScience+BusinessMediaNewYork2013117118W.Hepr
8、oblemsincludingdyslipidemia,insulinresistance,anddiabetes(7).Incontrasttorelativelyuncommonlipodystrophy,however,thelastthre
