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

Area of Science:

• Immunology
• Hematology
• Cell Biology

Background:

• Myeloid cell leukemia sequence 1 (Mcl-1) is an intracellular antiapoptotic factor.
• Mcl-1 is essential for mast cell survival in vitro.
• Genetic manipulation of Mcl-1 can eliminate specific hematopoietic cell populations in vivo.

Purpose of the Study:

• To investigate the role of Mcl-1 in mast cell and basophil development and survival in vivo.
• To generate a mouse model for studying mast cell and basophil function in allergic inflammation.

Main Methods:

• Generation of C57BL/6 mice with Cre recombinase expressed under the carboxypeptidase A3 (Cpa3) promoter (Cpa3-Cre).
• Conditional deletion of the Mcl-1 gene in Cpa3-Cre mice (Mcl-1(fl/fl)).
• Analysis of mast cell and basophil populations, and assessment of allergic inflammatory responses (passive cutaneous anaphylaxis, chronic allergic inflammation, passive systemic anaphylaxis).

Main Results:

• Cpa3-Cre; Mcl-1(fl/fl) mice showed a severe deficiency (92%-100%) in mast cells and a marked reduction (58%-78%) in basophils across various tissues.
• Other hematopoietic cell populations remained largely unaffected.
• These mice exhibited reduced tissue swelling and leukocyte infiltration in mast cell- and IgE-dependent allergic inflammation models.
• Mice were protected from IgE-dependent passive systemic anaphylaxis.

Conclusions:

• Mcl-1 is essential for normal mast cell and basophil development and survival in vivo.
• The generated Cpa3-Cre; Mcl-1(fl/fl) mouse model is a valuable tool for investigating the roles of mast cells and basophils in health and disease.
• Mcl-1 deletion effectively ablates mast cells and basophils, facilitating studies on their contribution to allergic inflammation.