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Spontaneous and Engineered Mutant Mice as Models for Experimental and Comparative Pathology: History, Comparison, and Developmental Technology

机译:自发和工程突变小鼠作为实验和比较病理学的模型:历史,比较和发展技术。

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Duringthelasthalf-centurypathologistshaveexploredthebiologicmechanismsassociatedwithinheritedhumanandveterinarydiseasesbyusinginbredandinbredmutant(spontaneous)strainsofmice.Thefirstsuccessfulgenetransfertomicebypronuclearinjectionoftheherpessimplexvirusthymidinekinasegeneandrabbitandhuman#59137;-globulingeneswasachievedintheearly1980s.Thisaccomplishmentwasfollowedafewyearslaterwiththecreationofamousebearingadisruptedhypoxanthinephosphoribosyltransferase(hrpt)gene(targetedmutationbasedonEScellblastocystinjection).Sincethen,hundredsofgeneticallyengineeredmodelsofbiomedicalimportancehavebeencreated.Theunprecedentedscaleandscopeofdevelopmentofengineeredmodelspresentgreatopportunitiesaswellasexperimentalchallengestotheinvestigator.Theaimofthepresentreviewistoprovideaframeworkofinformationonengineeredmousemodelsfromtheperspectiveofexperimentalandcomparativepathologyresearch.Sectionsinclude:1)abriefhistoricalaccountofthedevelopmentofmousemodelsofdisease,withincreasingprogressionofgeneticrefinementasrepresentedbyinbred(spontaneous)andcongenic(targeted)mutantstrainsofmice;2)asynopsisofspontaneousandtargetedmutations,withanecdotalexamplesofexpressionofindividualgenesandinteractionsbetweenmultiplemutantgenes;3)selectedexamplesoftargetedmutationsofinteresttodevelopmentalandcancerbiologistsandimmunologists;4)anoverviewofthetechnologyofdevelopmentoftransgenicmice;and5)anintroductiontoon-linedatabaseresourcesofcurrentmulti-speciesgenomicinformation.
机译:Duringthelasthalf-centurypathologistshaveexploredthebiologicmechanismsassociatedwithinheritedhumanandveterinarydiseasesbyusinginbredandinbredmutant(自发)strainsofmice.Thefirstsuccessfulgenetransfertomicebypronuclearinjectionoftheherpessimplexvirusthymidinekinasegeneandrabbitandhuman#59137; -globulingeneswasachievedintheearly1980s.Thisaccomplishmentwasfollowedafewyearslaterwiththecreationofamousebearingadisruptedhypoxanthinephosphoribosyltransferase(HRPT)基因(targetedmutationbasedonEScellblastocystinjection).Sincethen,hundredsofgeneticallyengineeredmodelsofbiomedicalimportancehavebeencreated.Theunprecedentedscaleandscopeofdevelopmentofengineeredmodelspresentgreatopportunitiesaswellasexperimentalchallengestotheinvestigator.Theaimofthepresentreviewistoprovideaframeworkofinformationonengineeredmousemodelsfromtheperspectiveofexperimentalandcomparativepathologyresearch.Sectionsinclude:1)abriefhistoricalaccountofthedevelopmentofmousemodelsofdisease,withincreasingprogressionofgeneticrefi nementasrepresentedbyinbred(自发)andcongenic(定位)mutantstrainsofmice; 2)asynopsisofspontaneousandtargetedmutations,withanecdotalexamplesofexpressionofindividualgenesandinteractionsbetweenmultiplemutantgenes; 3)selectedexamplesoftargetedmutationsofinteresttodevelopmentalandcancerbiologistsandimmunologists; 4)anoverviewofthetechnologyofdevelopmentoftransgenicmice; AND5)anintroductiontoon-linedatabaseresourcesofcurrentmulti-speciesgenomicinformation。

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