A Genome-Wide Screen for Asthma-Associated Quantitative Trait Loci in a Mouse Model of Allergic Asthma

Abstract

Asthma is the most common illness of childhood, affecting one child in seven in the UK. Asthma has a genetic basis, but genetic studies of asthma in humans are confounded by uncontrolled environmental factors, varying penetrance and phenotypic pleiotropy. An animal model of asthma would offer controlled exposure, limited and consistent genetic variation, and unlimited size of sibships. Following immunization and subsequent challenge with ovalbumin, the Biozzi BP2 mouse shows features of asthma, including airway inflammation, eosinophil infiltration and non-specific bronchial responsiveness. In order to identify genetic loci influencing these traits, a cross was made between BP2 and BALB/c mice, and a genome-wide screen carried out in the F₂ progeny of the F₁ intercross. Five potentially linked loci were identified, four of which corresponded to human regions of syntenic homology that previously have shown linkage to asthma-associated traits.