A novel in vivo inducible dendritic cell ablation model in mice
A novel in vivo inducible dendritic cell ablation model in mice
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DOI：
10.1016/j.bbrc.2010.05.157
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发表时间：
2010-07-02
影响因子：
3.1
通讯作者：
Takeda, Kiyoshi
中科院分区：
文献类型：
--
作者：
Okuyama, Megumi;Kayama, Hisako;Takeda, Kiyoshi
树突状细胞（DC）通过其摄取和呈递抗原参与T细胞活化。使用在CD 11 c/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DC的体内功能。然而，CD 11 c（+）细胞是含有几个DC亚群的异质群体。因此，每个DC亚群的体内功能仍有待阐明。在这里，我们描述了一种新的诱导型DC消融模型，其中DTR表达在Cre介导的终止盒切除后在CD 11 c/Itgax启动子下诱导（CD 11 c-iDTR）。将CD 11 c-iDTR小鼠与在巨细胞病毒立即早期增强子-鸡β-肌动蛋白杂合启动子控制下表达Cre重组酶的CAG-Cre转基因小鼠杂交，产生了DTR选择性表达于CD 11 c（+）细胞中的小鼠（iDTR Delta小鼠）。在iDTR Delta小鼠中，我们成功地在体外去除了骨髓来源的DC中的CD 11 c（+）细胞，并在体内去除了脾脏中的CD 11 c（+）细胞。该小鼠品系将是使用转基因小鼠品系产生缺乏DC的特定亚群的小鼠的有用工具，其中Cre基因由DC亚群特异性启动子表达。(C)2010年爱思唯尔公司All rights reserved.
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 (iDTR Delta mice). We successfully deleted CD11c(+) cells in bone marrow-derived DCs in vitro and splenic CD11c(+) cells in vivo after DT treatment in iDTR Delta 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. (C) 2010 Elsevier Inc. All rights reserved.