title: Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl-1fl/fl mice.
abstract: 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.
authors: Department of Pathology, Stanford University School of Medicine, CA 94305-5324, USA.
authors: Jennifer N
authors: JN
authors: Lilla
authors: Ching-Cheng
authors: CC
authors: Chen
authors: Kaori
authors: K
authors: Mukai
authors: Maya J
authors: MJ
authors: BenBarak
authors: Christopher B
authors: CB
authors: Franco
authors: Janet
authors: J
authors: Kalesnikoff
authors: Mang
authors: M
authors: Yu
authors: Mindy
authors: M
authors: Tsai
authors: Adrian M
authors: AM
authors: Piliponsky
authors: Stephen J
authors: SJ
authors: Galli
mesh_terms: D000818:Animals; D001491:Basophils / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D043422:Carboxypeptidases A / Q000235:genetics / Q000378:metabolism*; D002452:Cell Count; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000235:genetics / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D007073:Immunoglobulin E; C045073:Cre recombinase; D019426:Integrases; D043422:Carboxypeptidases A; C503326:Cpa3 protein, mouse