Postnatal liver growth and regeneration are independent of c-myc in a mouse model of conditional hepatic c-myc deletion 英文参考文献.docVIP

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Postnatal liver growth and regeneration are independent of c-myc in a mouse model of conditional hepatic c-myc deletion 英文参考文献.doc

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Postnatal liver growth and regeneration are independent of c-myc in a mouse model of conditional hepatic c-myc deletion 英文参考文献

Sandersetal.BMCPhysiology2012,12:1 /1472-6793/12/1 RESEARCH ARTICLE OpenAccess Postnatallivergrowthandregenerationare independentofc-mycinamousemodelof conditionalhepaticc-mycdeletion JenniferASanders1*,ChristophSchorl2,3,AjayPatel4,JohnMSedivy2,3 andPhilipAGruppuso1,2 Abstract Background:Thetranscriptionfactorc-mycregulatesgenesinvolvedinhepatocytegrowth,proliferation, metabolism,anddifferentiation.Ithasalsobeenassignedrolesinliverdevelopmentandregeneration.Inprevious studies,wemadetheunexpectedobservationthatc-Mycproteinlevelsweresimilarinproliferatingfetalliverand quiescentadultliverwithc-Mycdisplayingnucleolarlocalizationinthelatter.Inordertoinvestigatethefunctional roleofc-Mycinadultliver,wehavedevelopedahepatocyte-specificc-mycknockoutmouse,c-mycfl/fl;Alb-Cre. Results:Liverweighttobodyweightratiosweresimilarincontrolandc-mycdeficientmice.Liverarchitecturewas unaffected.Conditionalc-mycdeletiondidnotresultincompensatoryinductionofothermycfamilymembersor inc-Myc’sbindingpartnerMax.Floxedc-mycdidhaveanegativeeffectonAlb-Creexpressionat4weeksofage. Toexplorethisrelationshipfurther,weusedtheRosa26reporterlinetoassayCreactivityinthec-mycfloxedmice. NosignificantdifferenceinAlb-Creactivitywasfoundbetweencontrolandc-mycfl/fl mice.c-mycdeficientmice werestudiedinanonproliferativemodeloflivergrowth,fastingfor48hrfollowedbya24hrrefeedingperiod. Fastingresultedinadecreaseinlivermassandliverprotein,bothofwhichrecoveredupon24hofrefeedingin thec-mycfl/fl;Alb-Creanimals.Therewasalsonoeffectofreducingc-myconrecoveryoflivermassfollowing2/3 partialhepatectomy. Conclusions:c-Mycappearstobedispensablefornormallivergrowthduringthepostnatalperiod,restorationof livermassfollowingpartialhepatectomyandrecoveryfromfasting. Background has a functional role in the coordination of cellular TheMycfamily includes three closely related genes, c- growthandproliferation.Theexpressionofc-mycis,in myc,L-myc,andN-myc,whichhavebeenshowntohave general,tightlyregulated.Prolifera