Quantitative trait loci controlling allergen-induced airway hyperresponsiveness in inbred mice

Identification of the genetic loci underlying asthma in humans has been ham pered by variability in clinical phenotype, uncontrolled environmental infl uences, and genetic heterogeneity. To circumvent these complications, the g enetic regulation of asthma-associated phenotypes was studied in a murine m odel. We characterized the strain distribution patterns for the asthma-rela ted phenotypes airway hyperresponsiveness (AHR), lung eosinophils, and oval bumin (OVA)-specific serum immunoglobulin (Ig) E induced by allergen exposu re protocols in A/J, AKR/J, BALB/cJ, C3H/HeJ, and C57BL/6J inbred strains a nd in (C3H/HeJ x A/J)F1 mice. Expression of AHR differed between strains an d was sometimes discordant with lung eosinophils or serum IgE. Furthermore, we identified two distinct quantitative trait loci (QTL) for susceptibilit y to allergen-induced AHR, Abhr1 (allergen-induced bronchial hyperresponsiv eness) (lod = 4.2) and Abhr2 (lod = 3.7), on chromosome 2 in backcross prog eny from A/J and C3H/HeJ mice. In addition, a QTL on chromosome 7 was sugge stive of linkage to this trait. These QTL differ from those we have previou sly found to control noninflammatory AHR in the same crosses. Elucidation o f the genes underlying these QTL will facilitate the identification of bioc hemical pathways regulating AHR in animal models of asthma and may provide insights into the pathogenesis of human disease.