NSG mouse - Wikipedia
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The NSG mouse (NOD scid gamma mouse) is a brand of immunodeficient laboratory mice, developed and marketed by Jackson Laboratory, which carries the strain ... NSGmouse FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch TheNSGmouse(NODscidgammamouse)isabrandofimmunodeficientlaboratorymice,developedandmarketedbyJacksonLaboratory,whichcarriesthestrainNOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ.NSGbrandedmiceareamongthemostimmunodeficientdescribedtodate.[1]NSGbrandedmicelackmatureTcells,Bcells,andnaturalkiller(NK)cells.[2]NSGbrandedmicearealsodeficientinmultiplecytokinesignalingpathways,andtheyhavemanydefectsininnateimmunity.[2][3]ThecompoundimmunodeficienciesinNSGbrandedmicepermittheengraftmentofawiderangeofprimaryhumancells,andenablesophisticatedmodelingofmanyareasofhumanbiologyanddisease.NSGbrandedmiceweredevelopedinthelaboratoryofDr.LeonardShultzatJacksonLaboratory,whichownstheNSGtrademark. Contents 1FeaturesofNSGmice 2ResearchapplicationsofNSGinclude 3References 4Notes 5Externallinks FeaturesofNSGmice[edit] Thegeneticbackground,derivedfrominbredNODmousestrainNOD/ShiLtJ,contributesreductionsininnateimmunitythatincludeanabsenthemolyticcomplementsystem,reduceddendriticcellfunction,anddefectivemacrophageactivity.[3]TheNOD/ShiLtJbackgroundalsocontributesanalleleoftheSirpagenethatrendersthebonemarrownicheverypermissivetocolonizationbyhumanhematopoieticstemcells.[4] ThePrkdcscidmutationa,commonlyknownas“scid”or“severecombinedimmunodeficiency”,essentiallyeliminatesadaptiveimmunity.[5]Prkdcscidisaloss-of-functionmutationinthemousehomologueofthehumanPRKDCgene,whichencodesaproteinthatresolvesDNAstrandbreaksthatoccurduringV(D)JrecombinationindevelopingTandBlymphocytes.[6]MicehomozygousforthemutationhaveseverelyreducednumbersofmatureTandBcells.[3][5]ThephenotypicpenetranceofPrkdcscidvariesamonginbredstrainbackgrounds,butthemutationismosteffectiveateliminatingadaptiveimmunityontheNODgeneticbackground.[3]DuetothePrkdcscidmutation,however,theNSGstrainshowshighsensitivitytoradiation,T-cellleakage,andincreasedincidenceofthymiclymphomaformation;assuch,thisstraincannotbeusedtopredictclinicalresponsetocertainanticancerdrugs,orforlong-termtransplantationstudies.[7][8] TheIl2rgtm1Wjltargetedmutationbisacompletenullmutationinthegeneencodingtheinterleukin2receptorgammachain(IL2Rγ,homologoustoIL2RGinhumans).[9]IL2Rγisacommoncomponentofthecellsurfacereceptorsthatbindandtransducesignalsfromsixdistinctinterleukins.SignalingthroughIL2Rγisrequiredforthedifferentiationandfunctionofmanyhematopoieticcells.[9]Notably,theabsenceofIL2RγblocksNKcelldifferentiation,andtherebyremovesamajorobstaclepreventingtheefficientengraftmentofprimaryhumancells.[2][5] ResearchapplicationsofNSGinclude[edit] Primaryhumanlungtumorxenograftsthatpreservethetumormicroenvironmentduringlong-termengraftment[10] Humanizedmodelforevaluationofpossiblecancercuringgenetherapy.[11] Modelsofacuteorchronicleukemiaestablishedusingcancercellscollectedfrompatients(Acompletelistofpublicationsisavailablehere) Ahighlysensitiveplatformforstudyingepithelial[12]andcancerstemcells[13] Establishingafunctional,humanizedimmunesystemfromengraftedhumanhematopoieticstemcells[14][15]andprogenitors[16] Humanizedmodelsforstudyinghuman-specificinfectiousdiseaseslikeHIV,[17]EpsteinBarrvirus,[18]malaria,[19]andDenguefever.[20][21]Humanizedmodelsalsoaidintestingnewtherapies[17] Studyingallograftrejectionafterpancreaticislettransplantationtherapyfortype1diabetes[22] References[edit] ^ShultzLD,IshikawaF,GreinerDL(2007)."Humanizedmiceintranslationalbiomedicalresearch".Nat.Rev.Immunol.7(2):118–130.doi:10.1038/nri2017.PMID 17259968.S2CID 7933096. ^abcShultzLD,LyonsBL,BurzenskiLM,et al.(2005)."HumanlymphoidandmyeloidcelldevelopmentinNOD/LtSz-scidIL2Rgammanullmiceengraftedwithmobilizedhumanhemopoieticstemcells"(PDF).J.Immunol.174(10):6477–89.doi:10.4049/jimmunol.174.10.6477.PMID 15879151. ^abcdShultzLD,SchweitzerPA,ChristiansonSW,et al.(1995)."MultipledefectsininnateandadaptiveimmunologicfunctioninNOD/LtSz-scidmice".J.Immunol.154(1):180–91.PMID 7995938. ^TakenakaK,PrasolavaTK,WangJC,et al.(2007)."PolymorphisminSirpamodulatesengraftmentofhumanhematopoieticstemcells".Nat.Immunol.8(12):1313–23.doi:10.1038/ni1527.PMID 17982459.S2CID 7874854. ^abcGreinerDL,HesseltonRA,ShultzLD(1998)."SCIDmousemodelsofhumanstemcellengraftment".StemCells.16(3):166–177.doi:10.1002/stem.160166.PMID 9617892. ^BluntT,FinnieNJ,TaccioliGE,et al.(1995)."DefectiveDNA-dependentproteinkinaseactivityislinkedtoV(D)JrecombinationandDNArepairdefectsassociatedwiththemurinescidmutation".Cell.80(5):813–23.doi:10.1016/0092-8674(95)90360-7.PMID 7889575. ^Pearson,T;Shultz,LD(2008)."Non-ObeseDiabetic-RecombinationActivatingGene-1(NOD-Rag1null)Interleukin(IL)-2ReceptorCommonGammaChain(IL2Rγnull)NullMice:ARadioresistantModelforHumanLymphohaematopoieticEngraftment".Clinical&ExperimentalImmunology.154(2):270–284.doi:10.1111/j.1365-2249.2008.03753.x.PMC 2612717.PMID 18785974. ^Fulop,GM;Phillips,RA(1990)."TheScidMutationinMiceCausesaGeneralDefectinDNARepair".Nature.347(6292):479–482.Bibcode:1990Natur.347..479F.doi:10.1038/347479a0.PMID 2215662.S2CID 4351206. ^abCaoX,ShoresEW,Hu-LiJ,et al.(1995)."Defectivelymphoiddevelopmentinmicelackingexpressionofthecommoncytokinereceptorgammachain".Immunity.2(3):223–38.doi:10.1016/1074-7613(95)90047-0.PMID 7697543. ^Simpson-AbelsonMR,SonnenbergGF,TakitaH,et al.(2008)."Long-termengraftmentandexpansionoftumor-derivedmemoryTcellsfollowingtheimplantationofnon-disruptedpiecesofhumanlungtumorintoNOD-scidIL2Rgamma(null)mice".J.Immunol.180(10):7009–18.doi:10.4049/jimmunol.180.10.7009.PMID 18453623. ^EscobarG,MoiD,RanghettiA,et al.(Jan2014)."GeneticengineeringofhematopoiesisfortargetedIFN-αdeliveryinhibitsbreastcancerprogression".Sci.Transl.Med.6(217):217.doi:10.1126/scitranslmed.3006353.PMID 24382895.S2CID 8430299. ^EirewP,StinglJ,RaoufA,et al.(2008)."Amethodforquantifyingnormalhumanmammaryepithelialstemcellswithinvivoregenerativeability".Nat.Med.14(12):1384–9.doi:10.1038/nm.1791.PMID 19029987.S2CID 205385845. ^QuintanaE,ShackletonM,SabelMS,FullenDR,JohnsonTM,MorrisonSJ(2008)."Efficienttumourformationbysinglehumanmelanomacells".Nature.456(7222):593–598.Bibcode:2008Natur.456..593Q.doi:10.1038/nature07567.PMC 2597380.PMID 19052619. ^IshikawaF,YasukawaM,LyonsB,et al.(2005)."DevelopmentoffunctionalhumanbloodandimmunesystemsinNOD/SCID/IL2receptor{gamma}chain(null)mice".Blood.106(5):1565–73.doi:10.1182/blood-2005-02-0516.PMC 1895228.PMID 15920010. ^GiassiLJ,PearsonT,ShultzLD,et al.(August2008)."ExpandedCD34+humanumbilicalcordbloodcellsgeneratemultiplelymphohematopoieticlineagesinNOD-scidIL2rgamma(null)mice".Exp.Biol.Med.(Maywood).233(8):997–1012.doi:10.3181/0802-RM-70.PMC 2757278.PMID 18653783. ^MajetiR,ParkCY,WeissmanIL(2007)."Identificationofahierarchyofmultipotenthematopoieticprogenitorsinhumancordblood".CellStemCell.1(6):635–645.doi:10.1016/j.stem.2007.10.001.PMC 2292126.PMID 18371405. ^abKumarP,BanHS,KimSS,et al.(2008)."Tcell-specificsiRNAdeliverysuppressesHIV-1infectioninhumanizedmice".Cell.134(4):577–86.doi:10.1016/j.cell.2008.06.034.PMC 2943428.PMID 18691745. ^StrowigT,GurerC,PlossA,et al.(2009)."PrimingofprotectiveTcellresponsesagainstvirus-inducedtumorsinmicewithhumanimmunesystemcomponents".J.Exp.Med.206(6):1423–34.doi:10.1084/jem.20081720.PMC 2715061.PMID 19487422. ^Jiménez-DíazMB,MuletT,VieraS,et al.(2009)."ImprovedmurinemodelofmalariausingPlasmodiumfalciparumcompetentstrainsandnon-myelodepletedNOD-scidIL2Rgammanullmiceengraftedwithhumanerythrocytes".Antimicrob.AgentsChemother.53(10):4533–6.doi:10.1128/AAC.00519-09.PMC 2764183.PMID 19596869. ^MotaJ,Rico-HesseR(2009)."Humanizedmiceshowclinicalsignsofdenguefeveraccordingtoinfectingvirusgenotype".J.Virol.83(17):8638–8645.doi:10.1128/JVI.00581-09.PMC 2738212.PMID 19535452. ^JaiswalS,PearsonT,FribergH,et al.(2009).UnutmazD(ed.)."Denguevirusinfectionandvirus-specificHLA-A2restrictedimmuneresponsesinhumanizedNOD-scidIL2rgammanullmice".PLOSONE.4(10):e7251.Bibcode:2009PLoSO...4.7251J.doi:10.1371/journal.pone.0007251.PMC 2749937.PMID 19802382. ^KingM,PearsonT,ShultzLD,et al.(2008)."AnewHu-PBLmodelforthestudyofhumanisletalloreactivitybasedonNOD-scidmicebearingatargetedmutationintheIL-2receptorgammachaingene".Clin.Immunol.126(3):303–14.doi:10.1016/j.clim.2007.11.001.PMID 18096436. Notes[edit] 1.^MouseGenomeInformaticsentryforPrkdcscid 2.^MouseGenomeInformaticsentryforIl2rgtm1Wjl Externallinks[edit] NSGstraindatasheetatTheJacksonLaboratory NSGdiscussionforum Categorizedlistofreferences Retrievedfrom"https://en.wikipedia.org/w/index.php?title=NSG_mouse&oldid=1043644208" Categories:Immunologymice Navigationmenu Personaltools NotloggedinTalkContributionsCreateaccountLogin Namespaces ArticleTalk English Views ReadEditViewhistory More Search Navigation MainpageContentsCurrenteventsRandomarticleAboutWikipediaContactusDonate Contribute HelpLearntoeditCommunityportalRecentchangesUploadfile Tools WhatlinkshereRelatedchangesUploadfileSpecialpagesPermanentlinkPageinformationCitethispageWikidataitem Print/export DownloadasPDFPrintableversion Languages TiếngViệt Editlinks
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