Development of Multiple Features of Antigen-Induced Asthma Pathology in a New Strain of Mast Cell Deficient BALB/c-KitW-Sh/W-Sh Mice

Rationale: Genetically mast cell (MC)-deficient mice are used to identify and quantify the contributions of MCs to various biological responses in vivo, such as defense against venoms, parasite immunity and allergic inflammation. However, despite the fact that scores of genes have been identified as modifiers of allergic inflammation, most MC-deficient models have been available only on a single genetic background.

Methods: We transferred the Kit^W-sh allele onto the BALB/c background to generate BALB/c MC-deficient mice (BALB/c-Kit^W-sh/W-sh). We examined in BALB/c-Kit^W-sh/W-sh mice models of allergic inflammation to which MCs substantially contribute in C57BL6-Kit^W-sh/W-shmice.

Results: BALB/c-Kit^W-sh/W-sh mice have dramatically reduced numbers of MCs (0-2% of wild type) in all tissues examined. In addition, BALB/c-Kit^W-sh/W-sh mice exhibited subtle hematologic differences compared to wild type mice, including splenomegaly with evidence of increased splenic hematopoiesis. In a model of acute allergic inflammation, IgE-dependent passive cutaneous anaphylaxis, both ear swelling and leukocyte infiltration were largely or entirely MC-dependent in BALB/c-Kit^W-sh/W-sh mice. In contrast, in two different models of chronic allergic airway inflammation to ovalbumin or house dust mite, airway hyperresponsiveness, lung inflammation, and airway remodeling developed robustly in MC-deficient BALB/c-Kit^W-sh/W-shmice.

Conclusions: These results support the conclusion that the importance of MC contributions in various models of allergic inflammation may be at least partially determined by genetic background.