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MGI Accession ID: MGI:3772787
J Number: J:131076
Other Accession IDs: Title: A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration.
Authors: Buch T; Heppner FL; Tertilt C; Heinen TJ; Kremer M; Wunderlich FT; Jung S; Waisman A
Journal: Nat Methods
Volume: 2
Issue: 6
Date: 2005 Jun
Year: 2005
Pages: 419-26
Review Status: Peer Reviewed

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.

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