Airway hyperresponsiveness (AHR) is a key physiological component of asthma. While AHR is inducible in experimental animal models by sensitization to antigen and can be potentiated by antigen challenge in sensitized humans, it is also evident in non-sensitized (naive) individuals. The genetic basis of this complex trait has remained elusive. Analysis of mice that demonstrate heritable naive airway hyperresponsiveness provides a means to identify its underlying molecular basis. We have previously used genetic mapping to identify quantitative trait loci (QTLs) that confer AHR. We have also used genetic and pharmacological analysis to demonstrate that this trait is mediated by mast cells. In this proposal, we plan to continue our investigation of the heritable loci that predispose to AHR using state-of-the-art genetic strategies, and to assess the role of mast cells in conferring the strain-specific AHR trait.

Public Health Relevance

Increased airway responsiveness to stimuli is a physiological component of human asthma. Genetic analysis of mice that demonstrate airway hyperresponsiveness as heritable trait provides a means to identify its underlying molecular basis, and potentially a method to treat it.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL105849-01
Application #
8022055
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Banks-Schlegel, Susan P
Project Start
2010-12-01
Project End
2014-11-30
Budget Start
2010-12-01
Budget End
2011-11-30
Support Year
1
Fiscal Year
2011
Total Cost
$472,841
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115