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Neuropathologic Findings Associated with Seizures in FVB Mice

机译:与FVB小鼠癫痫发作相关的神经病理学发现

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TheFVBmouseisusedextensivelyintransgenicresearchbecauseofitsdefinedinbredbackground,superiorreproductiveperformance,andprominentpronuclei,whichfacilitatemicroinjectionofgenomicmaterial.Seizuresassociatedwithaknownmutationandseizure-susceptibleinbredstrainsarewelldocumentedinmice;however,totheauthors'knowledge,seizuresintheFVBstrainhavenotbeenevaluated.AffectednonmanipulatedFVB/N(n=5)andtransgenicFVB/Nmicegenerated,usingeightunrelatedtransgenicconstructs(n=63),weresubmittedforpathologicexamination.Mostcasesweredetectedduringroutineobservationsinanimalrooms;however,seizureinductionbytailtattooing,furclipping,andfirealarmshasbeenobserved.Themajorityofmicewerefemale(62of68),withmeanageof5.8months(range,2to16months).Observationsmadeduringseizurepresentationin12of68miceincludedfacialgrimace,chewingautomatism,ptyalismwithmattingofthefuroftheventralaspectoftheneckand/orforelimbs,andclonicconvulsionsthatfrequentlyprogressedtotonicconvulsionsanddeath.Fourmiceweredeadatpresentation,withmattingofthefuroftheneckandforelimbs.Theremainderofthemicehadnonspecificsignsofdisease,suchaslethargy,moribundity,ormattingofthefur.Vendorandin-houseanimalhealthsurveillancereportsindicatedthatmicewereseronegativetoallmurinepathogens.Resultsofgrosspathologicexaminationwereunremarkable.Microscopicfindingswerelimitedtothebrainandliver.Inallmice,neuronalnecrosiswaspresentinthecerebralcortex,hippocampus,andthalamus.Concurrentastrocytehypertrophy,asevidencedbyanincreaseinglialfibrillaryacidicproteinstaining,wasdetected.Acutecoagulativenecrosisofcentrilobularhepatocyteswaspresentintheliverofsomecases(19of68).Infectiveagentswerenotdetectedinselectedbrainspecimenssubmittedforelectronmicroscopyorinbrainandliverspecimensevaluatedbyuseofspecialstains.Cytopathologiceffectwasnotobservedin3T3,Vero,andBHK-21celllinesinoculatedwithbrainandliverspecimens.Theischemicneuronalnecrosisobservedinthesemiceisconsistentwithlesionsassociatedwithstatusepilepticusinhumans.Thehepatocellularchangesareinterpretedtobeagonalandassociatedwithterminalhypoxiainseizuringanimals.Theseresultsprovideevidenceofapreviouslyunrecognized,oftenlethalepilepticsyndromeinFVBmicethatmayhaveamajorimpactontransgenicresearchandotherdisciplinesusingthismousestrain.
机译:TheFVBmouseisusedextensivelyintransgenicresearchbecauseofitsdefinedinbredbackground,superiorreproductiveperformance,andprominentpronuclei,whichfacilitatemicroinjectionofgenomicmaterial.Seizuresassociatedwithaknownmutationandseizure-susceptibleinbredstrainsarewelldocumentedinmice;然而,totheauthors'knowledge,seizuresintheFVBstrainhavenotbeenevaluated.AffectednonmanipulatedFVB / N(N = 5)andtransgenicFVB / Nmicegenerated,usingeightunrelatedtransgenicconstructs(N = 63),weresubmittedforpathologicexamination.Mostcasesweredetectedduringroutineobservationsinanimalrooms;然而,seizureinductionbytailtattooing,furclipping,andfirealarmshasbeenobserved多数小鼠(68人中的62人)的平均寿命为5.8个月(2至16个月)。在68位小鼠的癫痫发作表现中观察到的包括面部表情,咀嚼自动主义,对政策和观点的粗暴对待,以及与之相似的倾向,并与之类似。 hefuroftheneckandforelimbs.Theremainderofthemicehadnonspecificsignsofdisease,suchaslethargy,濒死,ormattingofthefur.Vendorandin-houseanimalhealthsurveillancereportsindicatedthatmicewereseronegativetoallmurinepathogens.Resultsofgrosspathologicexaminationwereunremarkable.Microscopicfindingswerelimitedtothebrainandliver.Inallmice,neuronalnecrosiswaspresentinthecerebralcortex,海马,andthalamus.Concurrentastrocytehypertrophy,asevidencedbyanincreaseinglialfibrillaryacidicproteinstaining,wasdetected.Acutecoagulativenecrosisofcentrilobularhepatocyteswaspresentintheliverofsomecases(19of68).Infectiveagentswerenotdetectedinselectedbrainspecimenssubmittedforelectronmicroscopyorinbrainandliverspecimensevaluatedbyuseofspecialstains.Cytopathologiceffectwasnotobservedin3T3,VERO,andBHK-21celllinesinoculatedwithbrainandliverspecimens.Theischemicneuronalnecrosisobservedinthesemiceisconsistentwithlesionsassociatedwithstatusepilepticusinhumans.Thehepatocellularchangesareinterpretedtobeagonaland这些结果提供了以前无法识别的FVB小鼠典型的癫痫综合症的证据,该研究可能对转基因研究有重大影响,并使用了抗震性菌株。

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