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Mouse genetic model for antigen-induced airway manifestations of asthma

Genes & Immunity volume 8, pages 28–34 (2007)Cite this article

Abstract

Allergic asthma is a genetically complex disease characterized by allergen-specific immunoglobulin (Ig)E, eosinophilic inflammation of the lungs and airway hyper-responsiveness to bronchospasmogenic stimuli. In this study, we compared 13 recombinant congenic (RC) mouse strains in an ovalbumin model of allergic asthma. Different intensities and types of responses are observed throughout the RC strains. Intensities range from resistance to asthma in CcS05, to a very severe bronchoconstrictive reaction upon methacholine challenge for the parental STS strain. All strains show a ‘modified’ Th2 response except CcS14, which shows a ‘true’ Th2 response. When data from all strains are pooled, airway reactivity shows significant correlations with the serum Ig levels and the levels of interleukin (IL)-4, IL-5 and IL-13 in the broncho-alveolar lavage (BAL), at low dosage of methacholine (below 25 mg/ml), whereas at high dosage airway reactivity only correlates with BAL neutrophil levels. This indicates that at least two different mechanisms are involved in the airway reactivity to methacholine. None of these correlations can be found in every individual strain, which demonstrates that the asthma traits in this mouse model are genetically dissociated and that the loci can be genetically mapped.

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Acknowledgements

We thank Professor Dr DS Postma and Dr GH Koppelman for their critical reviews of the manuscript and Dr HM Boezen for her help on the statistics. This work is supported by research grants (AF99.23 and AF03.55) of the Dutch Asthma Foundation (NAF).

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Author notes

  1. P V Jeurink

    Present address: Department of Cell biology and immunology, University of Wageningen, Wageningen, The Netherlands

  2. B Piavaux and P V Jeurink: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Laboratory Allergology and Pulmonary Diseases, Groningen University Medical Centre, Groningen University, Groningen, The Netherlands

    B Piavaux & A J M Van Oosterhout

  2. Department of Pharmacology and Pathophysiology, Faculty of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

    P V Jeurink, P C Groot & G A Hofman

  3. Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY, USA

    P Demant

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  1. B Piavaux
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Correspondence to A J M Van Oosterhout.

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Piavaux, B., Jeurink, P., Groot, P. et al. Mouse genetic model for antigen-induced airway manifestations of asthma. Genes Immun 8, 28–34 (2007). https://doi.org/10.1038/sj.gene.6364354

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