The long-term goal of this research is to increase understanding of basic genetic mechanisms controlling susceptibility of children to asthma following viral infection and allergen exposure. The research will use a rat model of virus-induced and allergen-accentuated asthma. Genetically-susceptible BN rats and resistant F344 rats will be studied following parainfluenza virus type 1 (Sendai) virus infection and repeated ovalbumin exposure.
The specific aims are: 1) To evaluate the relative contributions of viral infection and recurrent airway allergen exposure during early life on the development of chronic airway inflammation and remodeling and airway hyperresponsiveness in atopic and non-atopic rats (BN and F344); 2) To identify genetic loci (quantitative trait loci-QTLs) controlling susceptibility to virus-induced and allergen-accentuated airway inflammation and asthma-like phenotypes using genome-wide scan and linkage analysis in (BN X F344) F1 and backcross rats; and 3) To develop congenic rat strains with chromosomal segments containing loci that control susceptibility to virus and allergen-induced asthma-like syndrome for subsequent fine chromosomal mapping studies and identification of specific genes controlling development of asthma-like phenotype.
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