6533b873fe1ef96bd12d4e46

RESEARCH PRODUCT

A novel in vivo inducible dendritic cell ablation model in mice

Kiyoshi TakedaHiroyuki SaigaMasahiro YamamotoKoji AtarashiMegumi OkuyamaTaishi KimuraAri WaismanHisako Kayama

subject

Genetically modified mouseT cellBiophysicsCD11cCre recombinaseMice Transgenicchemical and pharmacologic phenomenaBiologyBiochemistryMiceAntigenIn vivomedicineAnimalsPromoter Regions GeneticMolecular BiologyIntegraseshemic and immune systemsDendritic CellsCell BiologyDendritic cellMolecular biologyIn vitroCD11c Antigenmedicine.anatomical_structureModels AnimalIntercellular Signaling Peptides and ProteinsHeparin-binding EGF-like Growth Factor

description

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.

yearjournalcountryeditionlanguage
2010-07-10Biochemical and Biophysical Research Communications
https://doi.org/10.1016/j.bbrc.2010.05.157