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RESEARCH PRODUCT
A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration.
Thorsten BuchFrank L. HeppnerChristine TertiltF. Thomas WunderlichMarcel KremerSteffen JungTobias J. A. J. HeinenAri WaismanAri Waismansubject
Genetically modified mouseCell SurvivalTransgeneT cellT-LymphocytesCellCre recombinaseApoptosisMice TransgenicReceptors Cell SurfaceBiologyBiochemistryCell LineMicemedicineAnimalsCell LineageDiphtheria ToxinReceptorMolecular BiologyDiphtheria toxinIntegrasesCell DifferentiationCell BiologyMolecular biologyRecombinant ProteinsOligodendrogliamedicine.anatomical_structureCell cultureIntercellular Signaling Peptides and ProteinsBiotechnologyHeparin-binding EGF-like Growth Factordescription
A new system for lineage ablation is based on transgenic expression of a diphtheria toxin receptor (DTR) in mouse cells and application of diphtheria toxin (DT). To streamline this approach, we generated Cre-inducible DTR transgenic mice (iDTR) in which Cre-mediated excision of a STOP cassette renders cells sensitive to DT. We tested the iDTR strain by crossing to the T cell- and B cell-specific CD4-Cre and CD19-Cre strains, respectively, and observed efficient ablation of T and B cells after exposure to DT. In MOGi-Cre/iDTR double transgenic mice expressing Cre recombinase in oligodendrocytes, we observed myelin loss after intraperitoneal DT injections. Thus, DT crosses the blood-brain barrier and promotes cell ablation in the central nervous system. Notably, we show that the developing DT-specific antibody response is weak and not neutralizing, and thus does not impede the efficacy of DT. Our results validate the use of iDTR mice as a tool for cell ablation in vivo.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2004-09-29 | Nature methods |