Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl-1fl/fl mice.
It has been reported that the intracellular antiapoptotic factor myeloid cell leukemia sequence 1 (Mcl-1) is required for mast cell survival in vitro, and that genetic manipulation of Mcl-1 can be used to delete individual hematopoietic cell populations in vivo. In the present study, we report the generation of C57BL/6 mice in which Cre recombinase is expressed under the control of a segment of the carboxypeptidase A3 (Cpa3) promoter. C57BL/6-Cpa3-Cre; Mcl-1(fl/fl) mice are severely deficient in mast cells (92%-100% reduced in various tissues analyzed) and also have a marked deficiency in basophils (58%-78% reduced in the compartments analyzed), whereas the numbers of other hematopoietic cell populations exhibit little or no changes. Moreover, Cpa3-Cre; Mcl-1(fl/fl) mice exhibited marked reductions in the tissue swelling and leukocyte infiltration that are associated with both mast cell- and IgE-dependent passive cutaneous anaphylaxis (except at sites engrafted with in vitro-derived mast cells) and a basophil- and IgE-dependent model of chronic allergic inflammation, and do not develop IgE-dependent passive systemic anaphylaxis. Our findings support the conclusion that Mcl-1 is required for normal mast cell and basophil development/survival in vivo in mice, and also suggest that Cpa3-Cre; Mcl-1(fl/fl) mice may be useful in analyzing the roles of mast cells and basophils in health and disease.
Pubmed ID: 22001390 RIS Download
Animals | Basophils | Blotting, Western | Carboxypeptidases A | Cell Count | Cells, Cultured | Chronic Disease | Female | Flow Cytometry | Hypersensitivity | Immunoglobulin E | Inflammation | Integrases | Leukocytes | Male | Mast Cells | Mice | Mice, Inbred C57BL | Mice, Knockout | Mice, Transgenic | Myeloid Cell Leukemia Sequence 1 Protein | Passive Cutaneous Anaphylaxis | Promoter Regions, Genetic | Proto-Oncogene Proteins c-bcl-2