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.

journal_name

Blood

journal_title

Blood

authors

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

doi

10.1182/blood-2011-03-343962

subject

Has Abstract

pub_date

2011-12-22 00:00:00

pages

6930-8

issue

26

eissn

0006-4971

issn

1528-0020

pii

blood-2011-03-343962

journal_volume

118

pub_type

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