Karyotypic normalcy and quasi-normalcy of developmentally totipotent mouse teratocarcinoma cells☆

摘要

Malignantmouseteratocarcinomacellsare,insomecases,abletoundergonormal,completedifferentiationafterinjectionintoblastocysts.Thusfar,onlythreelinesa€”ofunrelatedorigina€”havebeenfound(allinthislaboratory)tobedevelopmentallytotipotentinblastocysttests.Thekaryotypesoftheselines,andtheirsomatic-andgerm-cellderivatives,wereinvestigatedbyG-bandingmethods,asapossiblecluetotheirdevelopmentalsuperiority.Thefirst,OTT6050(129strain),isanembryo-derivedinducedtumormaintainedasanascitestransplantline.Itsstemcells(fromembryoidbodya€?coresa€?)have40chromosomesinthemodalclass,whichcomprisestwosubclasses:oneallnormalandonewithametacentricchromosome(isochromosome-8).However,mosaicanimalsfrominjectedblastocystshaveonlythenormalsubclassintheirteratocarcinomaderivedcells;allareofXYmalesexchromosometype.PresenceoftheYchromosomewasverifiedaftertransmissionthroughthegermlineoftwofertilemosaicmales,intheirF1maleprogeny.Thesecondteratocarcinomaline,72484-395(LTstrain),isaspontaneousovariansolidtumormaintainedbysubcutaneoustransplantation.Karyotypesofcellsfromthetumor,andalsoofteratocarcinoma-derivedcellsinmosaicanimals,werenormalandofXXfemalesexchromosometype.KaryotypesoftheF1progeny,fromtumor-straingermcellsofafertilemosaicfemale,werealsonormal.Thethirdline,NG2(129strain),isamutantclonalinvitrolinedeficientinhypoxanthinephosphoribosyltransferase.Itoriginatedfromanembryo-derivedexperimentaltumor(OTT5568)thatwasestablishedinculture(PSA1line);theculturewasthenmutagenizedandselectedfor6-thioguanineresistance.TheNG2lineprovedtobequasi-normal,withonlytwokaryotypicanomalies:trisomyofchromosome6andXOfemalesexchromosomeconstitution.Thus,developmentaltotipotencyinallthreelines,includingonemaintainedinvitro,isaccompaniedbykaryotypicnormalcyornear-normalcy.Otherculturelinesreportedtobeaneuploidhavenotyetgivenevidenceoftotipotency.Karyotypicnormalcymaythereforehavepredictivevalueusefulinchoosingteratocarcinomalineswithrelativelyhighdevelopmentalprospects.Thisisofimportanceinidentifyingthosemutantlinesthatwouldbepromisingcandidatesforintroduction,viablastocystinjection,ofspecificmutantgenesintomice.