2007 Fiscal Year Final Research Report Summary
The Basic Research for Establishing the Genetic Tasting of Bronchial Asthma
Project/Area Number |
18590527
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Laboratory medicine
|
Research Institution | Nagoya University |
Principal Investigator |
KAWABE Tsutomu Nagoya University, Department of Medical Technology, Associate Professor (20378219)
|
Co-Investigator(Kenkyū-buntansha) |
OHNO Tamio Nagoya University, Institute for Laboratory Animal Research, Associate Professor (90293620)
|
Project Period (FY) |
2006 – 2007
|
Keywords | Bronchial Asthma / Genetic Meting / Recombinant Inbred Strain / Consomic Mice |
Research Abstract |
Background: Asthma is regarded as a multifactorial inflammatory disorder arising as a result of inappropriate immune responses to common environmental antigens in genetically-susceptible individuals. However, the precise molecular genetic basis has been unknown. Objective: We sought to map candidate genes underlying biological responses to induce asthma using murine recombinant inbred (RI) and consomic strains. Methods: Using the SMXA RI strains, we assessed the three asthma-related phenotypes, airway hyperresponsiveness (AHR), eosinophil infiltration and allergen-specific serum IgE. Results: Quantitative trait locus (QTL) analysis revealed that a significant locus for AHR (genome-screen P < 0.05) was detected on chromosome 17. For eosinophil infiltration, significant loci were detected on chromosomes 9 and 16. Although we could not detect any significant loci for allergen-specific serum IgE, four suggestive loci (genome-screen P<0.5) were detected on chromosomes 10, 17 (two QTLs), and 19. We established consomic strains by chromosomal substitution and confirmed that chromosomes 17 and 19 contained candidate genes for allergen-specific serum IgE. Conclusion: We detected the genetic susceptibility loci, which regulate three asthma-related phenotypes separately. Our results suggested that different genetic mechanisms regulate these asthma-related phenotypes. Clinical implications: Genetic analyses using murine RI and consomic strains would enhance our understanding of the molecular mechanisms of asthma in human.
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Research Products
(68 results)