International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


Groot PC
Utrecht University

Co-Authors: 1) Jeurink P V, 1) Hofman G A, 1) Nijkamp F P, 2) Demant P, 1) Van Oosterhouta A J M
Institutions: 1) Utrecht University; 2) RPCI, Buffalo

Allergic asthma is a heterogeneous and genetically complex disease characterized by allergen-specific IgE, eosinophilic airway inflammation and hyperresponsiveness to bronchospasmogenic stimuli. We have used the Recombinant Congenic Strains of mice to facilitate the mapping of genes controlling these asthma traits. We compared 19 CcS/Dem strains, which each carry a random set of 12.5% of genes from the Th1-responder strain STS and 87.5% from the Th2-responder strain BALB/c. Mice were sensitized with ovalbumin (OVA) and repeatedly challenged by inhalation of OVA aerosol. Before and after OVA challenges, serum was obtained and airway responsiveness to nebulized methacholine (1.5-50 mg/ml) determined. Bronchoalveolar lavage (BAL) was performed and number of leukocytes and Th2 cytokinelevels were determined.

Although serum levels of OVA-specific IgE after challenge differ strongly between strains, only the parental strain STS did not show elevated IgE levels. CcS/Dem strains 5, 11, 12, 15 and 16 do not display significant airway hyperresponsiveness after OVA inhalation compared to responsiveness before challenge. In addition, CcS/Dem-5 has the lowest serum OVA-IgE levels and very low numbers of eosinophils in BAL which makes this an "asthma" resistant strain. It can be concluded that there is no correlation between serum IgE levels, the number of BAL eosinophils and airway hyperresponsiveness, i.e. CcS/Dem-12 displays "normal" airway eosinophilia but resistance to the induction of hyperresponsiveness. These data demonstrate that different asthma traits like IgE, eosinophilia and hyperresponsiveness are genetically dissociated in the mouse and that the loci segregating in the RCS-strains can thus be genetically mapped.

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