基因敲除模式小鼠的饲养与交配

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1、基因敲除模式小鼠的饲养与交配Whatareweusuallyusing?Painforlaboratorymicerevealedin'human'facialexpressionsGeneticallyEngineeredMouseModelsResourceGiftTransgenicKnockoutMadebyyourownKnockinMadebyBiocytogenGeneralprinciplesforbreedingFundamentalsofMouseReproductionSexualmaturity:6~8weeksReproductivelifespan:7

2、~8monthsFertilityGestation:18~21daysGenerationtime:12weeksLittersize:2~12pups/litterWeaningage:18~28daysBreedingPerformanceFactorsHybridvigor---more,larger,andhealthierlittersthaninbredstrains.Strain-specificbehaviors---AggressivebehaviorsorpoormothersMutationsandtransgeneeffects---Embryonicleth

3、al,orinfertilityorreducedfertilityOptimizingBreedingPerformanceReplacebreedersregularlyReplacenon-productivebreeders~60daysMatemiceearlyUseexperiencedmalesKeepaccuratebreedingrecordsOptimizingBreedingPerformanceLitterfosteringDeterminingpregnancyMatingnumerousfemalessimultaneouslyManagingSmallCo

4、loniesMaintainaminimumofsixbreedingpairsKeeptheagerangeofyourbreedersbetweentwoandeightmonthsoldRetaintwogenerationsofastrain,anddonoteliminateoneuntilthenextoneisproducingMonitorbreedingperformancecloselyConsidercryopreservingastrainBreedingSchemesChoosingaBreedingSchemeWhatgenotypesdoIneed?mos

5、tefficientwaytoproducethem?Willappropriatecontrolsbeavailable?geneticbackgroundHowaregenotypesidentified?phenotype?molecularassay(e.g.PCR)?WhataboutLinkage?X-linkedormultiplegenes?Reproductiveissues(sterility)Phenotypeissues(lethality)SimpleBreedingSchemes+/-+/+HeterozygousWildtype+/-+/++/-Heter

6、ozygousWildtype50%50%wildtypeKnockoutSimpleBreedingSchemes+/-+/-HeterozygousHeterozygous-/-+/-+/+HomozygousHeterozygousWildtype25%50%25%SimpleBreedingSchemes+/--/-HeterozygousHomozygous+/--/-HeterozygousHomozygous50%50%BackcrossingbreedingN1N#=backcrossgenerationnumberF#=brotherXsistergeneration

7、numberComplexBreedingSchemesTransgenicmiceTransgenicmice•Foundermice:transgenicmicethatdevelopfromtheinjectedeggs•Transgeniclines:derivedfromthesefoundersBreedingSchemesfortransgenicmiceGenotypingstrategyTg-FTg/++/+Heterozyg