A novel in vivo inducible dendritic cell ablation model in mice

Biochem Biophys Res Commun. 2010 Jul 2;397(3):559-63. doi: 10.1016/j.bbrc.2010.05.157.

Abstract

Dendritic cells (DCs) are involved in T cell activation via their uptake and presentation of antigens. In vivo function of DCs was analyzed using transgenic mouse models that express diphtheria toxin receptor (DTR) or the diphtheria toxin-A subunit (DTA) under the control of the CD11c/Itgax promoter. However, CD11c+ cells are heterogeneous populations that contain several DC subsets. Thus, the in vivo function of each subset of DCs remains to be elucidated. Here, we describe a new inducible DC ablation model, in which DTR expression is induced under the CD11c/Itgax promoter after Cre-mediated excision of a stop cassette (CD11c-iDTR). Crossing of CD11c-iDTR mice with CAG-Cre transgenic mice, expressing Cre recombinase under control of the cytomegalovirus immediate early enhancer-chicken beta-actin hybrid promoter, led to the generation of mice, in which DTR was selectively expressed in CD11c+ cells (iDTRDelta mice). We successfully deleted CD11c+ cells in bone marrow-derived DCs in vitro and splenic CD11c+ cells in vivo after DT treatment in iDTRDelta mice. This mouse strain will be a useful tool for generating mice lacking a specific subset of DCs using a transgenic mouse strain, in which the Cre gene is expressed by a DC subset-specific promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11c Antigen / genetics
  • Dendritic Cells / immunology*
  • Heparin-binding EGF-like Growth Factor
  • Integrases / genetics
  • Intercellular Signaling Peptides and Proteins / genetics
  • Mice
  • Mice, Transgenic
  • Models, Animal*
  • Promoter Regions, Genetic

Substances

  • CD11c Antigen
  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Cre recombinase
  • Integrases