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
Bloodjournal_title
Bloodauthors
Lilla JN,Chen CC,Mukai K,BenBarak MJ,Franco CB,Kalesnikoff J,Yu M,Tsai M,Piliponsky AM,Galli SJdoi
10.1182/blood-2011-03-343962subject
Has Abstractpub_date
2011-12-22 00:00:00pages
6930-8issue
26eissn
0006-4971issn
1528-0020pii
blood-2011-03-343962journal_volume
118pub_type
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