title: Genetic variation determines mast cell functions in experimental asthma.
abstract: Mast cell-deficient mice are a key for investigating the function of mast cells in health and disease. Allergic airway disease induced as a Th2-type immune response in mice is employed as a model to unravel the mechanisms underlying inception and progression of human allergic asthma. Previous work done in mast cell-deficient mouse strains that otherwise typically mount Th1-dominated immune responses revealed contradictory results as to whether mast cells contribute to the development of airway hyperresponsiveness and airway inflammation. However, a major contribution of mast cells was shown using adjuvant-free protocols to achieve sensitization. The identification of a traceable genetic polymorphism closely linked to the Kit(W-sh) allele allowed us to generate congenic mast cell-deficient mice on a Th2-prone BALB/c background, termed C.B6-Kit(W-sh). In accordance with the expectations, C.B6-Kit(W-sh) mice do not develop IgE- and mast cell-dependent passive cutaneous anaphylaxis. Yet, unexpectedly, C.B6-Kit(W-sh) mice develop full-blown airway inflammation, airway hyperresponsiveness, and mucus production despite the absence of mast cells. Thus, our findings demonstrate a major influence of genetic background on the contribution of mast cells in an important disease model and introduce a novel strain of mast cell-deficient mice.
authors.affiliation: Institute for Immunology, Medical Center, Johannes Gutenberg University, Mainz D-55131, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Becker
authors.forename: Sebastian
authors.initials: S
authors.lastname: Reuter
authors.forename: Pamela
authors.initials: P
authors.lastname: Friedrich
authors.forename: Fatma
authors.initials: F
authors.lastname: Doener
authors.forename: Anastasija
authors.initials: A
authors.lastname: Michel
authors.forename: Tobias
authors.initials: T
authors.lastname: Bopp
authors.forename: Matthias
authors.initials: M
authors.lastname: Klein
authors.forename: Edgar
authors.initials: E
authors.lastname: Schmitt
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schild
authors.forename: Markus P
authors.initials: MP
authors.lastname: Radsak
authors.forename: Bernd
authors.initials: B
authors.lastname: Echtenacher
authors.forename: Christian
authors.initials: C
authors.lastname: Taube
authors.forename: Michael
authors.initials: M
authors.lastname: Stassen
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016535:Bronchial Hyperreactivity; D002452:Cell Count; D007249:Inflammation; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D020297:Mice, Congenic; D011110:Polymorphism, Genetic; D018418:Th2 Cells