基因敲除与基因沉默-吕学诜

,,　(佳木斯大学,黑龙江佳木斯154007):基因打靶;基因敲除;基因沉默:Q785　:A　:1008-0104(2009)05-0065-01　　(geneknockout)(genesilencing)80～90,,。,,RNA(RNAi)。。,。1　(genetargeting)DNA。2080[1,2],、,,、、。、、、、,,。,,、、。MarioR.Capecchi,OliverSmithiesMartinJ.Evans2007[3]。20,,(EmbryonicStemcell,ES)(somaticcell);、(geneknockin)、、、。1.1　(geneknockout),。:①;②DNA;③;④。:①(completeknock-out);②;③——(genetrapping);④(“HitandRun”、“TagandExchange”)[4]。,。DNA,DNA(zinc-fingerDNA-bindingdomain),。;,,[5]。1.2　(geneknockin),,,。,,[6,7]。,,、,,。,,,。2　(genesilencing),DNA。,DNA、(transcriptionalgenesilencing,TGS),(post-transcriptionalgenesilencing,PTGS),RNA,RNA、(co-suppression)、(quelling)、RNA(RNAi)RNA(miRNA)。RNA,RNA[8]。RNA(RNAinterference,RNAi)、RNA(double-strandedRNA,dsRNA)、mRNA,。,,,。2006AndrewZ.FireCraigC.Mello,RNAi[9];RNA(MicroRNA,miRNA)、22ntRNA[9]。、,。miRBase()20092miRNA8619,695。miRNA,,miRNA。,miRNA[10],miRNA[11]。3　,“”DNA,“”。,(66)·65·HEILONGJIANGMEDICINEANDPHARMACYOct.2009,Vol.32No.5　　　　　　　　　　　　　　　　　　　　　89,,(佳木斯大学附属第一医院消化内科,黑龙江佳木斯154003):消化性溃疡;健康教育:R573.1;R193　:B　:1008-0104(2009)05-0066-02　　(pepticulcer,PU)、、、—Meckel。,,(gastriculcer,GS)(duodenunulcer,DU)[1]。,,。,、,5%[2]。,,,,。891,。1　1.1　892007-01～2007-05,ICD-10,30,35,24,1。56,33,17～68(38.5)。:10,45,34。2。45,44,、、(P0.05)。,。1.2　,,。(),。(),,。(65),。DNA,,。(geneknockdown),。,。,,。。。,、、、DNA。。,RNAi,,。,RNAishRNA、。,RNAi。DNA,。/,。miRNA,,miRNA。:[1]ThomasKR,CapecchiMR.Site-directedmutagenesisbygenetargetinginmouseembryo-derivedstemcells[J].Cell,1987,51(3):5035[2]DoetschmanT,GreggRG,MaedaN,etal.TargettedcorrectionofamutantHPRTgeneinmouseembryonicstemcells[J].Nature,1987,330(6148):576-578[3][4]MullerU.Tenyearsofgenetargeting:targetedmousemutants,fromvectordesigntophenotypeanalysis[J].Mech-Dev,1999,82(1-2):3-21[5]SantiagoY,ChanE,LiuPQ,etal.Targetedgeneknockoutinmammaliancellsusingengineeredzinc-fingernucleases[J].ProcNatlAcadSciUSA,2008,105(15):5809-5814[6]TateishiS,NiwaH,MiyazakiJ,etal.EnhancedgenomicinstabilityanddefectivepostreplicationrepairinRAD18knockoutmouseembryonicstemcells[J].MolCellBiol,2003,23(2):474-481[7]KerkhofsS,DenayerS,HaelensA,etal.Androgenreceptorknockoutandknock-inmousemodels[J].JMolEndocrinol,2009,42(1):11-17[8]SunBK,TsaoH.SmallRNAsindevelopmentanddisease[J].JAmAcadDermatol,2008,59(5):725-737[9]BartelDP.MicroRNAs:genomics,biogenesis,mechanism,andfunction[J].Cell,2004,116(2):281-297[10]SelbachM,SchwanhausserB,ThierfelderN,etal.WidespreadchangesinproteinsynthesisinducedbymicroRNAs[J].Nature,2008,455(7209):58-63[11]XiaoC,RajewskyK.MicroRNAcontrolintheimmunesystem:basicprinciples[J].Cell,2009,136(1):26-36(:2009-05-14)·66·　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　200910325