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Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl-1fl/fl mice

Lilla, Jennifer N., Chen, Ching-Cheng, Mukai, Kaori, BenBarak, Maya J., Franco, Christopher B., Kalesnikoff, Janet, Yu, Mang, Tsai, Mindy, Piliponsky, Adrian M., Galli, Stephen J.·2011·Blood
DOI 10.1182/blood-2011-03-343962
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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-1fl/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-1fl/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-1fl/fl mice may be useful in analyzing the roles of mast cells and basophils in health and disease.

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Research works printed but not linked: 37

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Metadata

Authors
Lilla, J. N., Chen, C.-C., Mukai, K., BenBarak, M. J., Franco, C. B., Kalesnikoff, J., Yu, M., Tsai, M., Piliponsky, A. M., & Galli, S. J.
Venue
Blood
Publisher
American Society of Hematology
Published
2011-12-22
Volume
118
Issue
26
Pages
6930-6938
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2011-03-343962
Cited by
203
References
2
Language
en

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