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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL061018-03
Application #
6184896
Study Section
Special Emphasis Panel (ZHL1-CSR-H (M3))
Project Start
1998-07-10
Project End
2003-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
3
Fiscal Year
2000
Total Cost
$319,798
Indirect Cost
Name
University of Florida
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
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Stone, Amy E S; Giguere, Steeve; Castleman, William L (2003) IL-12 reduces the severity of Sendai virus-induced bronchiolar inflammation and remodeling. Cytokine 24:103-13
Cai, Xuezhong; Castleman, William L (2003) Early high expression of IP-10 in F344 rats resistant to Sendai virus-induced airway injury. Am J Physiol Lung Cell Mol Physiol 285:L1263-9