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• W2248463987 abstract "Mast cells are well known effector cells in allergic disorders. In the recent years, however, mast cells were demonstrated to play pivotal roles in initiating and modulating innate and adaptive immune responses. The animal models available until today for the investigation of mast cell functions are primarily the Kit-mutant KitW/Wv and KitWsh/Wsh mouse strains. These mice are devoid of mast cells and can be reconstituted with mast cells from gene deficient mice. The phenotypic abnormalities, apart from mast cell deficiency, e.g. the profound perturbation of the hematopoietic system, however, limit the utility of these strains. Aiming at new models of mast cell-specific gene inactivation in vivo and of mast cell-deficiency, the Cre/loxP system was applied to allow Cre-mediated mutagenesis selectively in mast cells. BAC (bacterial artificial chromosome) transgenic animals were successfully generated that display Cre expression under the control of either the Mcpt5 or Mcpt6 promoter. Cre-mediated recombination as assessed by reporter gene expression in Mcpt5-Cre or Mcpt6-Cre R26R-EYFP double positive mice was found to be highly efficient in peritoneal and skin mast cells, but was not found in hematopoietic cell populations other than mast cells. Thus, the new mast cell-specific Cre transgenic mouse lines will provide useful tools for the investigation of mast cell-specific functions of individual genes. Furthermore, the Mcpt5-Cre strain was used to establish a new model for inducible ablation of mast cells in adult mice. By crossing this line to the iDTR strain, which expresses the high affinity diphtheria toxin receptor (DTR) after Cre-mediated deletion of a stop element, mast cells were rendered diphtheria toxin (DT) sensitive. DT treatment of Mcpt5-Cre iDTR double positive mice resulted in successful ablation of connective tissue type mast cells (CTMC), but not of mucosal mast cells (MMC). The depletion of CTMC resulted in significant reduction of a passive, systemic anaphylactic response demonstrating that this system for mast cell ablation represents a useful model for the investigation of mast cell functions during immune responses. Interestingly, the repopulation of the peritoneal cavity and the skin with mast cells after DT-mediated mast cell depletion followed a very slow kinetic with a noteworthy recurrence of peritoneal mast cells three months after DT treatment. Skin mast cells do not return significantly within a period of four months. Thus, the long persistence of the mast cell-depleted state allows the application of this system for long-term experiments and should provide new insights into the mechanisms of mast cell homeostasis and recruitment." @default.
• W2248463987 created "2016-06-24" @default.
• W2248463987 creator A5082558527 @default.
• W2248463987 date "2009-01-01" @default.
• W2248463987 modified "2023-09-27" @default.
• W2248463987 title "Novel tools for mast cell research: Mast cell-specific Cre-mediated gene inactivation and inducible ablation of mast cells in vivo" @default.
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