Plethysmography Phenotype QTL in Mice Before and After Allergen Sensitization and Challenge

Kelada, Samir N.  P.

doi:10.1534/g3.116.032912

Title: Plethysmography Phenotype QTL in Mice Before and After Allergen Sensitization and Challenge

Journal Article · Fri Jul 22 00:00:00 EDT 2016 · G3

DOI:https://doi.org/10.1534/g3.116.032912· OSTI ID:1378559

Kelada, Samir N. P. ^[1]

Univ. of North Carolina, Chapel Hill, NC (United States)

Allergic asthma is common airway disease that is characterized in part by enhanced airway constriction in response to nonspecific stimuli. Genome-wide association studies have identified multiple loci associated with asthma risk in humans, but these studies have not accounted for gene–environment interactions, which are thought to be important factors in asthma. To identify quantitative trait loci (QTL) that regulate responses to a common human allergen, we applied a house dust mite mouse (HDM) model of allergic airway disease (AAD) to 146 incipient lines of the Collaborative Cross (CC) and the CC founder strains. We employed a longitudinal study design in which mice were phenotyped for response to the bronchoconstrictor methacholine both before and after HDM sensitization and challenge using whole body plethysmography (WBP). There was significant variation in methacholine responsiveness due to both strain and HDM treatment, as reflected by changes in the WBP parameter enhanced pause. We also found that distinct QTL regulate baseline [chromosome (Chr) 18] and post-HDM (Chr 19) methacholine responsiveness and that post-HDM airway responsiveness was correlated with other features of AAD. Finally, using invasive measurements of airway mechanics, we tested whether the Chr 19 QTL affects lung resistance per se using C57BL/6J mice and a consomic strain but found that QTL haplotype did not affect lung resistance. We conclude that aspects of baseline and allergen-induced methacholine responsiveness are associated with genetic variation, and that robust detection of airway resistance QTL in genetically diverse mice will be facilitated by direct measurement of airway mechanics.

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Research Organization:: University of North Carolina, Chapel Hill, NC (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

OSTI ID:: 1378559

Journal Information:: G3, Vol. 6, Issue 9; ISSN 2160-1836

Publisher:: Genetics Society of AmericaCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 9 works

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Title: Plethysmography Phenotype QTL in Mice Before and After Allergen Sensitization and Challenge

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