Retroviral Elements and Their Hosts Insertional Mutagenesis in the Mouse Germ Line 英文参考文献.docVIP

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Retroviral Elements and Their Hosts Insertional Mutagenesis in the Mouse Germ Line 英文参考文献.doc

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Retroviral Elements and Their Hosts Insertional Mutagenesis in the Mouse Germ Line 英文参考文献

Review RetroviralElementsandTheirHosts: InsertionalMutagenesisintheMouse GermLine Irina A.Maksakova, Mark T.Romanish, Liane Gagnier, Catherine A.Dunn, Louie N.van de Lagemaat, Dixie L.Mager* ABSTRACT importanttounderstandthemutageniceventsaffectingthis speciesandhowtheydifferfromthoseinhumans.This articleexaminesmouseERVsandotherLTRretroelements, focusingoninsertionalmutagenesisofthegermline.Forthe purposesofthisreview,LTRretroelements,whichamplifyvia intracellularretrotransposition,andtrueexogenous retroviruses,whichamplifybyextracellularinfectionsand retrotransposition,willbeconsideredtogetheras‘‘ERVs’’as theyhaveacommonevolutionaryorigin[13].Wediscuss mutationalmechanismsofdifferentfamiliesofERVs, illustratingsigni?cantdifferencesintheireffectsongenes. WealsodiscusshostresponsestocurtailERVactivityand,in somecases,toadoptERVsfornormalcellfunctions.Finally, wepresenttheviewthatinbredmiceareinatransitorystate inwhichERVsarenotatequilibriumwiththeirhostgenome. T heinbredmouseisaninvaluablemodelforhuman biologyanddisease.Nevertheless,whenconsidering geneticmechanismsofvariationanddisease,itis importanttoappreciatethesigni?cantdifferencesinthe spectraofspontaneousmutationsthatdistinguishthese species.Whileinsertionsoftransposableelementsare responsibleforonly;0.1%ofdenovomutationsinhumans, the?gureis100-foldhigherinthelaboratorymouse.This strikingdifferenceislargelyduetotheongoingactivityof mouseendogenousretroviralelements.Herewebrie?y reviewmouseendogenousretroviruses(ERVs)andtheir in?uenceongeneexpression,analyzemechanismsof interactionbetweenERVsandthehostcell,andsummarize thevarietyofmutationscausedbyERVinsertions.The prevalenceofmouseERVactivityindicatesthatthegenome ofthelaboratorymouseispresentlybehindinthe‘‘arms race’’againstinvasion. PrevalenceofERV-InducedMouseInsertional Mutations Present-dayactivitiesaremarkedlydifferentbetween humanandmouseERVs.Arecentreviewlists48TEinsertion mutationsinhuman[17],andestimatesofthefrequencyof novelhumanTEinsertionsrangefr