A novel in vivo inducible dendritic cell ablation model in mice |
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Authors: | Megumi Okuyama Hisako Kayama Koji Atarashi Hiroyuki Saiga Taishi Kimura Ari Waisman Kiyoshi Takeda |
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Affiliation: | a Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan b WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan c Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany |
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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 (iDTRΔ mice). We successfully deleted CD11c+ cells in bone marrow-derived DCs in vitro and splenic CD11c+ cells in vivo after DT treatment in iDTRΔ 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. |
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Keywords: | DCs, dendritic cells DTR, diphtheria toxin receptor hbEGF, heparin-binding EGF-like growth factor cDCs, conventional DCs DTA, diphtheria toxin-A subunit pDCs, plasmacytoid DCs PE, phycoerythrin FITC, fluorescein isothiocyanate ES, embryonic stem BMDCs, bone marrow-derived dendritic cells |
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