Rescue of embryonic cells homozygous for a lethal haplotype of the T/t complex: tw12☆

[摘要] AseriesofrecessivemutationswhicharrestembryonicdevelopmentarelocatedwithintheT/tregionofchromosome17inthemouse.Toassesswhetherthesemutationscausedeathinspecificdifferentiatingcellsorinallcellsoftheembryo,weremovedtheembryoniccellsfromnormaldevelopmentalconstraintsandattemptedtogrowthemectopicallyinvivoandinvitro.Wehavesucceededinproducingteratomasandteratocarcinomasbytransplantationofinnercellmassesfromblastocystsoftw12+andtw12tw12genotypes.Theabilityofembryoniccellstogrowastumorswasnotaffectedbytheirgenotype;7ofthe17tumorswerehomozygousfortw12,7wereheterozygous,and3couldnotbeanalyzed.Virtuallyallthetumorsofbothgenotypescontainedderivativesofallthreegermlayers.Neuroepithelialandmaturenervoustissuewaspresentinallhomozygoustumorsandallexceptoneheterozygoustumor.However,nocartilageorbonewasfoundin5of5tw12homozygoustumors,whilebothtissueswerepresentin3of4tw12heterozygoustumors.Thisobservationiscompatiblewiththeabnormalitiescharacteristicoftw12tw12embryos,whichshowverylocalizedeffectsinnervoustissueandmoregeneraleffectsonboneandcartilageformation.Cellsderivedfromhomozygoustumorswerecapableofatleastlimitedgrowthincultureandacelllinehasbeenderivedfromoneofthem.Thep63/6.9amarkerproteinwasusedtodeterminethepresenceofthetw12haplotypeinthetumorandculturedcells.Weconcludethatthelethalityassociatedwiththetw12haplotypeisduetolethalityofspecificcells,andnotallcelltypes.

[学科分类] 生物科学（综合）