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.
Pubmed ID: 15908920 RIS Download
Mesh terms: Animals | Apoptosis | Cell Differentiation | Cell Line | Cell Lineage | Cell Survival | Diphtheria Toxin | Heparin-binding EGF-like Growth Factor | Integrases | Intercellular Signaling Peptides and Proteins | Mice | Mice, Transgenic | Oligodendroglia | Receptors, Cell Surface | Recombinant Proteins | T-Lymphocytes
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