Genetic model of high and non-responder ige phenotypes in inbred mice: Two dominant, independently segregating, mendelian genes control allergen-specific ige production

Production of allergen-specific IgE is controlled by multiple genetic loci. Initial studies by Marsh et al. (Science 1994, 264,1152) indicated that IL-4 gene did not segregate with the allergen-specific pathogenic IgE antibodies in humans. Genetic study of rodent IgE production in inbred mice eliminates genetic diversity, and properly selected strains also avoid variations due to quantitative trait loci. Thus murine model was employed herein. IgE high responder BALB/c, and low and nonresponder, i.e., SJL and SJA inbred mice, respectively, were examined for Mendelian genes governing "all-or none levels of allergen-specific IgE. Two dominant, independently segregating Mendelian genes were uncovered: The ratio of responder and nonresponder individuals was 3 to 1 in 175 backcross progeny of (BALB/cxSJA)F1 to SJA; and was 15 to 1 in F2 intercrosses of 126 (BALB/cxSJA)F1xF1, as well as 88 (BALB/cxSJL)F1xF1. Results were highly significant by x2 test and contingency table analyses. We will present segregation analysis on dominant genes for IgE production vs polymorphic microsatellite DMA markers bordering IL-4, IL-13 duster as well as IFN-v and IL-12 genes. Moreover we will attempt to scan at 25 centimorgan distance to localize the two dominant IgE responder genes by the Mapmaker Program.