CD11c-DTR/GFP transgenic line 57 has the CD11c promoter (Itgax) directing expression of a diphtheria toxin receptor - enhanced green fluorescent protein (DTR/EGFP) fusion protein to dendritic cell populations. Line 57 has more than 20 copies of the CD11c-DTR/GFP transgene inserted into the 1700016L21Rik locus on chromosome 1 (80448681-80455738 bp [Build GRCm38/mm10]).
Unmanipulated NOD congenic Itgax-DTR/EGFP (Cd11c-DTR) transgenic mice are viable, normal in size and develop spontaneous diabetes similar to NOD/ShiLtJ. All splenic CD8+ and CD8- DC express EGFP and are diphtheria toxin (DT) sensitive. Upon DT administration, mice harboring this transgene are transiently depleted of dendritic cell (DC) populations. Immunohistochemical and flow cytometric analysis reveals EGFP expression and DT-inducible depletion of CD11chigh DC in spleen, lymph node, lung, liver and lamina propria tissues, as well as the defined macrophage subpopulations of the alveolar, lamina propria, metallophillic and marginal zone. Rapid reduction of CD11c+ DC populations induced by intraperitoneal injection of DT persists for approximately 2 days, after which the cell population gradually recovers. While transient DC depletion was not associated with sign of illness or long-term defects, repeated DT induction induces an acute spike in the production of IFN-gamma and TNF-alpha and is lethal to the mouse. Long term depletion of this cell population without toxicity can be achieved by the generation of mixed irradiation chimeras. Irradiated NOD mice reconstituted with CD11c-DTR bone marrow treated long term with DT to ablate DC failed to develop insulitis.
CD11c-DTR/GFP transgenic mice are useful in studies of the specific role of dendritic cells in the immune response, specifically type 1 diabetes.
