title: A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration.
abstract: 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.
authors.affiliation: Laboratory for Molecular Immunology, Institute for Genetics, University of Cologne, D-50931 Cologne, Germany. thorsten.buch@uni-koeln.de
authors.forename: Thorsten
authors.initials: T
authors.lastname: Buch
authors.forename: Frank L
authors.initials: FL
authors.lastname: Heppner
authors.forename: Christine
authors.initials: C
authors.lastname: Tertilt
authors.forename: Tobias J A J
authors.initials: TJ
authors.lastname: Heinen
authors.forename: Marcel
authors.initials: M
authors.lastname: Kremer
authors.forename: F Thomas
authors.initials: FT
authors.lastname: Wunderlich
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D004167:Diphtheria Toxin / Q000494:pharmacology*; D066257:Heparin-binding EGF-like Growth Factor; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004167:Diphtheria Toxin; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C045073:Cre recombinase; D019426:Integrases