University of Tasmania
Browse

File(s) under permanent embargo

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

journal contribution
posted on 2023-05-17, 12:20 authored by Nawijn, MC, Piavaux, BJA, Jeurink, PV, Gras, R, Reinders, MA, Stearns, T, Simon James FooteSimon James Foote, Hylkema, MN, Groot, PC, Korstanje, R, Van Oosterhout, AJM
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.

History

Publication title

American Journal of Respiratory Cell and Molecular Biology

Volume

45

Pagination

295-303

ISSN

1535-4989

Department/School

Menzies Institute for Medical Research

Publisher

American Thoracic Society

Place of publication

1740 Broadway, New York, USA, NY, 10019-4374

Rights statement

Copyright 2011 The American Thoracic Society

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

Usage metrics

    University Of Tasmania

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC