Mammalian Genome

, Volume 21, Issue 1–2, pp 28–38 | Cite as

Identification of novel chromosomal regions associated with airway hyperresponsiveness in recombinant congenic strains of mice

  • Pierre Camateros
  • Rafael Marino
  • Anny Fortin
  • James G. Martin
  • Emil Skamene
  • Rob Sladek
  • Danuta RadziochEmail author


Airway responsiveness is the ability of the airways to respond to bronchoconstricting stimuli by reducing their diameter. Airway hyperresponsiveness has been associated with asthma susceptibility in both humans and murine models, and it has been shown to be a complex and heritable trait. In particular, the A/J mouse strain is known to have hyperresponsive airways, while the C57BL/6 strain is known to be relatively refractory to bronchoconstricting stimuli. We analyzed recombinant congenic strains (RCS) of mice generated from these hyper- and hyporesponsive parental strains to identify genetic loci underlying the trait of airway responsiveness in response to methacholine as assessed by whole-body plethysmography. Our screen identified 16 chromosomal regions significantly associated with airway hyperresponsiveness (genome-wide P ≤ 0.05): 8 are supported by independent and previously published reports while 8 are entirely novel. Regions that overlap with previous reports include two regions on chromosome 2, three on chromosome 6, one on chromosome 15, and two on chromosome 17. The 8 novel regions are located on chromosome 1 (92–100 cM), chromosome 5 (>73 cM), chromosome 7 (>63 cM), chromosome 8 (52–67 cM), chromosome 10 (3–7 cM and >68 cM), and chromosome 12 (25–38 cM and >52 cM). Our data identify several likely candidate genes from the 16 regions, including Ddr2, Hc, Fbn1, Flt3, Utrn, Enpp2, and Tsc.


Parental Strain Methacholine Airway Hyperresponsiveness Airway Responsiveness Potential Candidate Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This research was supported by grants from the Strategic Program for Asthma Research (SPAR) and the Canadian Institutes of Health Research (CIHR) awarded to Dr. D. Radzioch, a grant from Genome Quebec/Genome Canada awarded to Dr. E. Skamene, and a grant from Emerillon Therapeutics. R. Sladek is a Chercheur-boursier of the Fonds de la recherche en santé du Québec and the recipient of a MGH 175th Anniversary Award from the Research Institute of the Montreal General Hospital Foundation. P. Camateros and R. Marino are both supported by CIHR Doctoral Awards.

Supplementary material

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(DOC 266 kb)


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Pierre Camateros
    • 1
  • Rafael Marino
    • 1
  • Anny Fortin
    • 2
  • James G. Martin
    • 1
    • 3
  • Emil Skamene
    • 1
  • Rob Sladek
    • 1
    • 4
  • Danuta Radzioch
    • 1
    • 5
    • 6
    Email author
  1. 1.Division of Experimental Medicine, Department of MedicineMcGill UniversityMontrealCanada
  2. 2.Department of BiochemistryMcGill UniversityMontrealCanada
  3. 3.Meakins-Christie LaboratoriesMcGill UniversityMontrealCanada
  4. 4.McGill University and Génome Québec Innovation CentreMontréalCanada
  5. 5.Department of Human GeneticsMcGill UniversityMontrealCanada
  6. 6.MGH-Research InstituteMontrealCanada

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