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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

Authors

  • Lilla JN
  • Chen CC
  • Mukai K
  • BenBarak MJ
  • Franco CB
  • Kalesnikoff J
  • Yu M
  • Tsai M
  • Piliponsky AM
  • Galli SJ

Journal

Blood

Publication Data

December 22, 2011

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI023990
  • Agency: NIAID NIH HHS, Id: AI070813
  • Agency: NCI NIH HHS, Id: CA009151
  • Agency: NCI NIH HHS, Id: CA072074
  • Agency: NHLBI NIH HHS, Id: HL087936
  • Agency: NHLBI NIH HHS, Id: K99 HL087936
  • Agency: NHLBI NIH HHS, Id: K99 HL087936-01
  • Agency: NHLBI NIH HHS, Id: K99 HL087936-02
  • Agency: NHLBI NIH HHS, Id: R00 HL087936
  • Agency: NHLBI NIH HHS, Id: R00 HL087936-03
  • Agency: NHLBI NIH HHS, Id: R00 HL087936-04
  • Agency: NHLBI NIH HHS, Id: R00 HL087936-05
  • Agency: NIAID NIH HHS, Id: T32 AI007290
  • Agency: NCI NIH HHS, Id: T32 CA009151

Mesh Terms

  • 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