小鼠的遗传学研究

ChineseBulletinofLifeSciences185200610Vol.18,No.5Oct.,20062100632010~20Q959.837.03;Q95-33AGeneticresearchofmouseLINZhao-Yu,GAOXiang*(ModelAnimalResearchCenterofNanjingUniversity,Nanjing210063,China)Abstract:ThehistoryofmousegeneticsstartedwhenmicestrainswereimportedfrompetfarmtoCastle’slaboratoryinHarvardUniversityaboutonehundredyearsago.Mousegenomeishighlyhomologoustohumanandcanbemodifiedbyvariousapproaches.Moreover,thousandsofinbredstrains,mutantstrainsand“tool”strainshavebeendeveloped.Therefore,mousehasbecomethekeymodelanimalfortheresearchofdevelopmentbiology,functionalgenomicsanddiseasemechanism.Nowthemousegenomeprojectwascompleted.MillionsofmicrosatellitemarkersandSNPsamongdifferentinbredmousestrainswereidentified.Theassaysforthephysiologyandbiochemistryphenotypesareconstantlyimproving,alongwiththecollec-tionofmoreandmoredata.Theseworksenabletheseveralprogramsforlargescalegenomemutagenesis,genetargeting,aswellasconstructingandanalyzingnewrecombinedinbredstrains.Theseprogramsmaybecomethemostimportantstudiesinthebiologyandmedicineresearchinthecomingdecades.Keywords:mouse;genomemanipulation;inbredstrains;phenotypemapping;diseasemodel1004-0374(2006)05-0437-052006-10-02(1985)(1963)*1(craniota)(Mammalia)(Rodentia)(Muridae)(Mus)(musculus)1902Castle[1]1909CastleLittleDBAColdSpringHarborLaboratoryTheJacksonLaboratory438C57BL/6C3HCBABALB/c4006000[2]1982PalmiterBrinster[3]EvansSmithiesCapecchiESDNA1987[4]1998Dolly[5]19902002C57BL/6j51621812[6]1kb[7~9]DNA[10~12][13]()(/)200513[14]4522.76200296%99%[6]5~1010(20~40g)4393(genometyping)(WesternNorthernSouthernBlot)RNA(RT-PCR)20RNADNAES(knock-out)(knock-in)440X20008000(chlorambucil)Ethylnitrosourea(ENU)[10]ENU7001ENUENUESDNADNA5%~10%(genetrap)(enhancertrap)(promotertrap)(β-LacZGFP)DNADNA[11~12]ESDNADNADNA(neoTK)100%;()2002630003floxCrefloxCreLoxPCreCreCreLoxPfloxCreGLP14414200120051003020009863140101.91000()200742005300(1%)[1]SilverLM.Mousegenetics:Conceptsandapplications[M].Oxford:OxfordUniversityPress,1995[2]MouseGenomeInformatics[EB/OL].[3]PalmiterRD,BrinsterRL,HammerRE,etal.Dramaticgrowthofmicethatdevelopfromeggsmicroinjectedwithmetallothionein-growthhormonefusiongenes.Nature,1982,300(5893):611~615[4]ThomasKR,CapecchiMR.Site-directedmutagenesisbygenetargetinginmouseembryo-derivedstemcells.Cell,1987,51(3):503~512[5]WakayamaT,PerryAC,ZuccottiM,etal.Full-termdevel-opmentofmicefromenucleatedoocytesinjectedwithcu-muluscellnuclei.Nature,1998,394(6691):369~374[6]BradleyA.Miningthemousegenome.Nature,2002,420(6915):512~514[7]LoveJM,KnightAM,McAleerMA,etal.TowardsconstructionofahighresolutionmapofthemousegenomeusingPCR-analysedmicrosatellites.NucleicAcidsRes,1990,18(14):4123~4130[8]Lindblad-TohK,WinchesterE,DalyMJ,etal.Large-scalediscoveryandgenotypingofsingle-nucleotidepolymor-phismsinthemouse.NatGenet,2000,24(4):381~386[9]CuppenE.Haplotype-basedgeneticsinmiceandrats.TrendsGenet,2005,21(6):318~322[10]HrabedeAngelisMH,FlaswinkelH,FuchsH,etal.Ge-nome-wide,large-scaleproductionofmutantmicebyENUmutagenesis.NatGenet,2000,25(4):444~447[11]FlossT,WurstW.Functionalgenomicsbygene-trappinginembryonicstemcells.MethodsMolBiol,2002,185:347~379[12]HorieK,KuroiwaA,IkawaM,etal.EfficientchromosomaltranspositionofaTc1/mariner-liketransposonSleepingBeautyinmice.ProcNatlAcadSciUSA,2001,98(16):9191~9196[13]CoxRD,BrownSD.Rodentmodelsofgeneticdisease.CurrOpinGenetDev,2003,13(3):278~283[14][EB/OL].://://