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Identification of the Mhc Region as an Asthma Susceptibility Locus in Recombinant Congenic Mice

Citation

Nawijn, MC and Piavaux, BJA and Jeurink, PV and Gras, R and Reinders, MA and Stearns, T and Foote, S and Hylkema, MN and Groot, PC and Korstanje, R and Van Oosterhout, AJM, Identification of the Mhc Region as an Asthma Susceptibility Locus in Recombinant Congenic Mice, American Journal of Respiratory Cell and Molecular Biology, 45, (2) pp. 295-303. ISSN 1535-4989 (2011) [Refereed Article]


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Copyright Statement

Copyright 2011 The American Thoracic Society

DOI: doi:10.1165/rcmb.2009-0369OC

Abstract

Mouse models of allergic asthma are characterized by airway hyperreactivity (AHR), Th2-driven eosinophilic airway inflammation, high allergen-specific IgE (anti-OVA IgE) levels in serum, and airway remodeling. Because asthma susceptibility has a strong genetic component, we aimed to identify new asthma susceptibility genes in the mouse by analyzing the asthma phenotypes of the Leishmania major resistant (lmr) recombinant congenic (RC) strains. The lmr RC strains are derived from C57BL/6 and BALB/c intercrosses and carry congenic loci on chromosome 17 (lmr1) and 9 (lmr2) in both backgrounds. Whereas the lmr2 locus on chromosome 9 contributes to a small background-specific effect on anti-OVA IgE and AHR, the lmr1 locusonchromosome17 mediatesa strong effectonTh2-driven eosinophilic airway inflammation and background-specific effects on anti-OVA IgE and AHR. The lmr1 locus contains almost 600 polymorphic genes. To narrowdownthis numberof candidate genes,we performed genome-wide transcriptional profiling on lung tissue from C.lmr1 RC mice and BALB/c control mice. We identified a small number of differentially expressed genes located within the congenic fragment, including a number of Mhc genes, polymorphic between BALB/c and C57Bl/6. The analysis of asthma phenotypes in the C.B10-H2b RC strain, carrying the C57Bl/6 haplotype of the Mhc locus in a BALB/c genetic background, reveals a strikingly similar asthma phenotype compared with C.lmr1, indicating that the differentially expressed genes located within the C.B10-H2b congenic fragment are the most likely candidate genes to contribute to the reduced asthma phenotypes associated with the C57Bl/6 allele of lmr1.

Item Details

Item Type:Refereed Article
Keywords:allergic asthma; quantitative trait locus; recombinant congenic mice; chromosome 17; mouse model
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Immunogenetics (incl. Genetic Immunology)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
Author:Foote, S (Professor Simon Foote)
ID Code:78364
Year Published:2011
Web of Science® Times Cited:3
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-06-22
Last Modified:2017-09-13
Downloads:0

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