A novel in vivo inducible dendritic cell ablation model in mice.
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.
Okuyama
Megumi
M
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Kayama
Hisako
H
Atarashi
Koji
K
Saiga
Hiroyuki
H
Kimura
Taishi
T
Waisman
Ari
A
Yamamoto
Masahiro
M
Takeda
Kiyoshi
K
D000818:Animals; D039521:CD11c Antigen / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D066257:Heparin-binding EGF-like Growth Factor; D019426:Integrases / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D011401:Promoter Regions, Genetic
D039521:CD11c Antigen; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; C045073:Cre recombinase; D019426:Integrases