Gene-environment interactions in asthma in mice and humans

National Human Genome Research Institute

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Abstract

We previously established a mouse model of dust mite-induced asthma that recapitulates the key features of human asthma, namely airway hyper-responsiveness, inflammation, and mucus production. By applying this model to a new mouse genetic reference population known as the Collaborative Cross (CC), we identified quantitative trait loci (QTL) for airway inflammation, specifically the numbers of macrophages (Chromosome (Chr) 17), eosinophils (Chr 11), and neutrophils (Chrs 2, 4, 7) in lung lavage fluid. At the same time, we measured lung gene expression in these mice and characterized the gene expression profiles by (1) identifying genes that are correlated with inflammation phenotypes and (2) mapping of expression QTL (eQTL). We mined these data and identified a high priority candidate gene for neutrophilic inflammation, and are now in the process of characterizing the function of this gene in the lung, specifically in response to immune stimuli. We are also in the process of evaluating the role of genetic variation in this gene in human population-based studies of allergic asthma through collaborations that are already underway with Drs. Cookson and Postma.