實驗動物學(xué)總論 (NXPowerLite)

實驗動物學(xué)總論一實驗動物和實驗用動物

（一）實驗動物(Laboratoryanimals)是指經(jīng)人工培育或人工改造，對其攜帶的微生物實行控制；遺傳背景明確，來源清楚，用于科學(xué)實驗、藥品、生物制品的生產(chǎn)和檢定及其他科學(xué)實驗的動物。（二）實驗用動物(Animalsforresearch；Experimentalanimals）所有用于科學(xué)實驗的動物統(tǒng)稱為實驗動物。包括實驗動物，野生動物，經(jīng)濟(jì)動物和觀賞動物。二實驗動物學(xué)的定義和范圍（一）定義

實驗動物學(xué)（Laboratoryanimalscience）是研究實驗動物和動物實驗的科學(xué)。（二）研究范圍1.實驗動物遺傳育種學(xué)（Laboratoryanimalgeneticbreedingscience）2.實驗動物微生物學(xué)和寄生蟲學(xué)（Laboratoryanimalmicrobiologyandparasitology）

3.實驗動物環(huán)境生態(tài)學(xué)（Laboratoryanimalenvironmentalecology）

4.實驗動物營養(yǎng)學(xué)（Laboratoryanimalnutriology）

（二）研究范圍(續(xù))5.實驗動物飼養(yǎng)管理（Laboratoryanimalhusbandry）6.實驗動物醫(yī)學(xué)（Laboratoryanimalmedicine）7.比較醫(yī)學(xué)（Comparativemedicine）8.動物實驗（Animalexperimentaltechniques）三實驗動物的重要性（一）實驗動物是生命科學(xué)研究的支撐條件之一

生命科學(xué)實驗研究的四個支撐條件----AEIR要素A：Animal：實驗動物；E：Equipment：儀器設(shè)備；I：Information：信息；R：Reagent：試劑；（二）實驗動物在生命科學(xué)研究中被廣泛應(yīng)用，很多重要的科研成果來源于實驗動物（三）實驗動物是人類的替身，起著“活的天秤”和“活的化學(xué)試劑”的作用（四）實驗動物工作實行法制化管理四實驗動物的分類

（一）傳統(tǒng)的動物學(xué)分類方法依據(jù)自然分類法，把整個生物，通常是用界(kingdom)、門(phylum)、綱(class)、目(order)、科(family)、屬(genus)、種(species)等劃分分類等級。以大家鼠為例，它屬于：脊椎動物門(phylumvertebrata)哺乳動物綱(classmammalia)嚙齒目(orderrodentea)鼠科(familymurinae)大家鼠屬(genusrattus)大家鼠種(species

rattusnorvegicus)學(xué)名：褐家鼠（大家鼠）(Rattusnorvegicus)多數(shù)情況下，根據(jù)不同目的進(jìn)行種下分類，把實驗動物劃分為不同品系。（二）按實際用途分類1、實驗動物2、經(jīng)濟(jì)動物（Economicalanimals），或稱家畜、家禽

3、野生動物（Wildanimals）

4、觀賞動物（Exihibitinganimals）（三）按遺傳學(xué)控制分類

根據(jù)基因的純合程度，把實驗動物分成下列四類：

1、近交系動物（Inbredstrainanimals）

2、突變系動物（Mutantstrainanimals）

3、雜交群動物（Hybridcolonyanimals）（雜交一代，F(xiàn)1代動物）

4、封閉群動物(Closedcolonyanimals)1、近交系動物（Inbredstrainanimals）又叫純系動物。是采用同胞兄妹或親子交配，連續(xù)繁殖20代以上所培育出來的遺傳上達(dá)到高度一致的動物群。

基因純合程度可達(dá)99.8%。①

主要指嚙齒動物；可出現(xiàn)近親交配衰退。②

親子交配與兄妹交配不能混用。③

親子交配時必須采用年輕的雙親同其子女交配。④

較大動物純種培育很難獲得成功，因為世代間隔較長，費用較大，所以成功率低。⑤

禽類和兔的血緣關(guān)系達(dá)到80%以上（相當(dāng)于兄妹交配四代）時，即可稱為近交系。

2、突變系動物（Mutantstrainanimals）具有特殊突變基因的品系動物，正常染色體基因發(fā)生突變，并具有各種遺傳缺陷的動物。在長期繁殖過程中，動物的子代突然發(fā)生變異，變異的基因位點又可遺傳下去，或者即使沒有明確的基因位點，經(jīng)淘汰和選育后，仍能維持其穩(wěn)定的遺傳性狀。這種變異并能繼續(xù)保持遺傳基因特性的品系動物，稱為突變系動物。如無胸腺裸鼠、無K細(xì)胞、或無K、無B、無巨噬細(xì)胞等裸鼠。用于免疫研究、移植實驗等。3、雜交群動物（Hybridcolonyanimals）（雜交一代，F(xiàn)1代動物）兩個近交品系動物之間進(jìn)行有計劃交配所獲得的第一代動物。例如：C57BL/6J×DBA/2→B6D2F1（B6為C57BL/6J的縮寫，D2為DBA/2的縮寫。）4、封閉群動物(Closedcolonyanimals)以非近親交配方式進(jìn)行繁殖生產(chǎn)的一個種群，在不從外部引入新的血緣條件，至少連續(xù)繁殖四代以上稱封閉群。封閉群又稱遠(yuǎn)交群。（四）按微生物學(xué)控制分類

1、無菌動物（Germfreeanimals，GF）體內(nèi)、外無任何可檢測出的活的微生物和寄生蟲的動物。來源于無菌手術(shù)剖腹取胎，飼養(yǎng)在無菌隔離器內(nèi)，人工喂乳或保姆代養(yǎng)培育而成。

悉生動物(Gnotobiotesanimals，GA)體內(nèi)攜帶有已知微生物的動物。這種動物來源于無菌動物，人為的投給已知的單菌、雙菌、三菌或多菌。這些均為已知菌，與無菌動物一樣，飼養(yǎng)在隔離器中。2、無特定病原體動物(Speceficpathogenfreeanimals，SPF）體內(nèi)不存在特定病原微生物和寄生蟲的的動物，簡稱SPF動物。是指無傳染病的健康動物。這種動物都是來自無菌動物或悉生動物，轉(zhuǎn)移到屏障系統(tǒng)中飼養(yǎng)。要在屏障系統(tǒng)環(huán)境設(shè)施中飼育繁殖和進(jìn)行實驗，要進(jìn)行嚴(yán)格消毒、檢疫、隔離并定期剖腹凈化。3、清潔動物(Cleananimals，CL)又稱最低限度疾病動物(Ginimaldiseaseanimals),體內(nèi)外不攜帶人畜共患的病原體或動物傳染病病原的動物，不能帶有體外寄生蟲和大部分體內(nèi)寄生蟲。4、普通動物（Conventionalanimals）

未經(jīng)積極的微生物學(xué)控制，飼養(yǎng)在開放衛(wèi)生環(huán)境里的動物。墊料和飼料和飲水一般不消毒，飲用普通自來水。

所謂普通動物也并不是對微生物沒有一定控制的一般動物，而是要求不帶能夠感染人的微生物和體外寄生蟲。這種動物只能供教學(xué)和一般實驗用。

根據(jù)新修訂的國家實驗動物微生物、寄生蟲質(zhì)量標(biāo)準(zhǔn)，我國將實驗大、小鼠分為三類即清潔級、無特定病原體級、無菌級（包括悉生動物）。其它品種實驗動物仍然分為普通級、清潔級、無特定病原體級、無菌級（包括悉生動物）四級。即從2002年5月1日起取消了普通級大、小鼠標(biāo)準(zhǔn)。TheJacksonLaboratory

In1929,Harvard-trainedgeneticistClarenceCookLittlefoundedTheJacksonLaboratory,basedonthethen-radicalideathatmicewerekeytounderstandingthegeneticbasisofhumandevelopment,diseasesanddisorders.Throughoutthe1900s,thatideawouldbecomeincreasinglycentraltotheprogressofbiomedicalresearch,reachingultimateconfirmationwhenthemouseand

humangenomesweresequencedattheturnofthecenturyandproveddefinitivelythatthetwospeciessharethevastmajorityoftheirgenes.【上海斯萊克實驗動物有限責(zé)任公司】【中國科學(xué)院上海實驗動物中心】【國家嚙齒類實驗動物種子中心上海分中心】AnimalCareandUse

Laboratoryanimalsareusedinbiomedicalresearchasmodelsforhumans.Observedbehavioralorphysiologicalchangesexhibitedbytheseanimals,whentheyareusedintheprotocol,areassumedtoberesponsestotheexperimentalprocedures.Ifnon-experimentalvariablescausedbyinadequatehousing,disease,orstressfromimproperhandlingareinadvertentlyintroducedintothestudytheycanelicitsimilarresponseswhichcouldskewthedataortotallyconfoundtheexperiment.Thesafeandeffectiveuseofanimalsinalaboratorysettingisanessentialelementofyourresearchactivities.

TheAnimalWelfareAct(AWA),andPHSPolicy

requirethatallAnimalUserscompletetrainingonthelaws,regulations,andproceduresassociatedwithanimalcareanduse.Thiscourseisdesignedtofulfillthatrequirement,providingaquickoverviewoftherelevantlawsandregulationscoveringuseofanimalsinalaboratorysetting,andtherecommendedproceduresforworkingwithspecificanimals.Thecourseincludespracticalandessentialinformationthatwillguideyouintheeverydaycareanduseofanimalsinyourlaboratoryenvironment.ImportanceofProperAnimalCareYourprimaryresponsibilitywhenworkingwithlaboratoryanimalsistotreatthemhumanely.Withthatinmind,themajorchallengeistomanagetheanimalsinawaythatminimizestheirexposuretopainanddistressandmaintainstheintegrityoftheirphysiologicalfunctionstofacilitatethegenerationofreliableresearchdata.Thiscoursewillteachyouhowthepropertreatmentofanimalscarriestheaddedbenefitofminimizingtheintroductionofunwantedvariablesintotheresearchprocess.ImportanceofProperAnimalCareYourcareandtreatmentofanimalsmustalsocomplywiththeappropriatelaws,regulations,andwithNIHpolicy.Manyoftheselaws,regulationsandpolicieswereenactedinresponsetopublicconcernaboutthetreatmentofanimalsintheresearchsetting.Consequently,yourobjectiveshouldbetotreatyouranimalsinamannerthatcomplieswiththeethicalandlegalimperativesprescribedforthehumanetreatmentoflaboratoryanimalsthatwillreflectpositivelyonNIHasaresearchinstitution.researchinstitution.LawsandRegulations:Themainregulations,policiesandguidelinesthatapplytoanimaluseatNIHare:TheAnimalWelfareAct(AWA)

ThePublicHealthServicePolicyonHumaneCareandUseofLaboratoryAnimals(PHSPolicy)

U.S.GovernmentPrinciplesfortheUtilizationandCareofVertebrateAnimalsUsedinTesting,Research,andTraining(GovernmentPrinciples)

GuidefortheCareandUseofLaboratoryAnimals(Guide)

NIHManual3040-2:AnimalCareandUseintheIntramuralProgramStructureandAccreditationTheDDIRdelegatestotheDirectoroftheOfficeofAnimalCareandUse(OACU)overallresponsibilityforensuringthattheACUprogramcomplieswithapplicablepoliciesandregulations.PainandDistressThereisalsoapragmaticpointofscientificlogicthatsupportsminimizingtheexposureofresearchanimalstoexperimentalpainordistress.Animalsrespondtopainanddistresswithchangesintheirnormalphysiologywhichcanskewdatabeingcollected.AlleviatingPainandDistressAnimals,likehumans,canbeexpectedtogenerateastressresponsetonovelstimuli.Handlinganimalsveryearlyinlife,evenasnew-borns,to"gentlethem"isaprocedurethathasbeenwidelyusedonavarietyofspeciestofamiliarizetheanimalswiththehandlingprocess.Whenanimalsaretrainedthiswaytoassociatehandlingwithpleasantcircumstancestheyaremuchlesslikelytogenerateastressresponselaterinlifewhentheyarehandled.AlternativesTheThreeRs:

Reduction:Reductionsinthenumbersofanimalsusedtoobtaininformationofacertainamountandprecision.Refinement:Decreaseintheincidenceorseverityofpainanddistressinthoseanimalsthatareused.Replacement:Substitutionofinsentientmaterialforanimalsorsubstitutionofalowerspecies,whichmightbelesssensitivetopainanddistress,forahigherspecies.MinimizingExposuretoDiseasewhenWorkingwithAnimalsStandardlaboratoryprotectiveclothingincludes:

Uniforms-Uniformsareclothing,suchassurgicalscrubsuitsandcoveralls,dedicatedforwearduringworkintheanimalfacility.Auniformshouldnotbewornoutsideoftheanimalfacilityorresearchsetting.Forexample,uniformsshouldnotbeworninpubliccafeterias,lecturehalls,andmedicalpatientcareareas.Gloves-Lightweightvinylorlatexglovespreventcontaminationoftheskinwithpathogensthatmaybeonanimals'bodiesoronsurfacessoiledbytheirexcreta.Labcoats-Disposablelabcoatsandcoverallsprotectstreetclothesfromcontaminationwithanimalpathogens.Labcoatsshouldnotbewornoutsideoftheanimalfacilityorresearchsetting.Forlongtermworkintheanimalfacility,auniformmaybesubstitutedforthesetypesofcoveringgarments.MucousMembraneProtection–Adeviceoracombinationofdevicessuchasfaceshieldsorsurgicalfacemaskscombinedwithprotectiveglassesorgoggles,worntoprotectthemouth,nose,andeyesfromsplashordropletcontamination.Thedegreeofprotectionneededvarieswiththespecificprocedurebeingconductedandshouldbeadjustedtotheleveloftheanticipatedrisk.Fullfaceshieldsprovidesplashprotectionforallofthefacialmucusmembranes.Partialmucousmembraneprotectionisprovidedbyusingonlyafacemaskandmaybeappropriatewhenthefecaloralrouteofcontaminationistheonlyconcern.ShoeCovering-Stretchbooties,usuallymadeofpaperorplastic,arewornoverstreetshoestopreventthetransferofpathogenicorganisms.Bootiesshouldnotbewornoutsideoftheanimalfacility.Dedicatedfootwearcanbesubstitutedforshoecoveringsduringlong-termactivities.Ifdedicatedshoesareworn,shoecoveringsmaybeusedtocovertheshoeswhenoutsidetheanimalfacility,buttheshoecoversmustberemovedonreturntothefacility.CageSystems

Cagesystemsthatmeetthegeneralrequirementsformaintenanceofnormalbodyfunctionsandprovidemoderateprotectionfromexposuretopathogensaredescribedas"conventional"cages.Conventionalcages,however,donotadequatelyprotectratsandmicefromairbornediseasestowhichtheyarehighlysusceptiblesocagesystemsthatarespeciallydesignedtoprovideextraprotectionfromthesepathogensareused.Rodentvirusesandotherairbornepathogensmaybetransportedbyclingingtodustparticlesandotherparticulatemattersuspendedintheairinsideandabovetheanimalcage.Theriskofexposuretotheseorganismsisreducedbyincreasingfreshaircirculatingaroundthecages,orfilteringtheair.waterSanitationFilteredAirUnit

ObservingandReportingProblemswithAnimalsWhileanimalhealthisthechargeoftheveterinarians,youwillhavearesponsibilitytoobserveandreportchangesinananimal'shealthandtoinformtheveterinarianoranimalfacilitymanagersothattheanimalcanbetreated.Immediateidentificationofsickorinjuredanimalsiscriticallyimportantinaresearchsettingbecausetheanimalsarecloselyconfined,andhousingspaceisfrequentlysharedbyseveralinvestigators.Infectiousdiseaseinonegroupofanimalscouldjeopardizealloftheanimalsintheroomorbuilding.SignsofIllnessandInjury:

Pickingupmice.

Whenpickingupmice,alwaysholdthemousebythebaseofthetail.Thiscanbedonewitheitherforcepsoryourfingers.DONOTpickmiceupbythetipofthetail.Ifyoupickamouseupbythetipofitstail,themousemayspinintightcircleswhenitsfeetlosecontactwiththecagesurface.Ifthishappens,thetipoftailcanbepulledoff.Additionally,amouseheldbythetipofitstailcan"climbupitstail"andbiteyou!Separatingmice/ratsbygender.

Separatingmice/ratsbygendercanbedifficult,especiallywhentheyareyoungandmales'testicleshavenotdescendedintothescrotum.Comparetherelativedistancebetweenanusandurinarypapilla.Thedistancebetweentheanusandtheurinarypapillaisgreaterinthemale.Thisphotographillustratesthatthemouseontherighthasthelesser(shorter)distancebetweentheanusandtheurinarypapilla,soitisthefemale.RestrainingRats.

Ratscanbecaughtandliftedbythebaseofthei