Okuyama Megumi, Kayama Hisako, Atarashi Koji, Saiga Hiroyuki, Kimura Taishi, Waisman Ari, Yamamoto Masahiro, Takeda Kiyoshi
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Biochem Biophys Res Commun. 2010 Jul 2;397(3):559-63. doi: 10.1016/j.bbrc.2010.05.157.
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.
树突状细胞(DCs)通过摄取和呈递抗原参与T细胞活化。利用在CD11c/Itgax启动子控制下表达白喉毒素受体(DTR)或白喉毒素A亚基(DTA)的转基因小鼠模型分析了DCs的体内功能。然而,CD11c+细胞是包含多个DC亚群的异质性群体。因此,每个DC亚群的体内功能仍有待阐明。在此,我们描述了一种新的可诱导DC消融模型,其中在Cre介导的终止盒切除后,在CD11c/Itgax启动子下诱导DTR表达(CD11c-iDTR)。将CD11c-iDTR小鼠与CAG-Cre转基因小鼠杂交,后者在巨细胞病毒立即早期增强子-鸡β-肌动蛋白杂交启动子控制下表达Cre重组酶,从而产生了DTR在CD11c+细胞中选择性表达的小鼠(iDTRDelta小鼠)。在iDTRDelta小鼠中进行DT处理后,我们成功地在体外删除了骨髓来源DC中的CD11c+细胞,并在体内删除了脾脏CD11c+细胞。该小鼠品系将成为一种有用的工具,用于利用转基因小鼠品系产生缺乏特定DC亚群的小鼠,其中Cre基因由DC亚群特异性启动子表达。