Gene expression in whole lung and pulmonary macrophages reflects the dynamic pathology associated with airway surface dehydration [left lobe only]

Scnn1b-Tg mice overexpress the beta subunit of the epithelial sodium channel (Scnn1b) in airway Club cells. The general phenotype of these mice is described in three published manuscripts (Mall et al. 2004, Nature Medicine, 10(5):487-93; Mall et al. 2008, Am J Respir Crit Care Med. 177(7):730-42; Livraghi-Butrico et al. 2012, Physiol. Genomics 44(8):470-84; and Livraghi-Butrico et al. 2012, Mucosal Immunology 5(4):397-408). Briefly, overexpression of the Scnn1b transgene in airway Club cells leads to hyperabsorption of sodium from the airway surface liquid, which causes airway surface liquid and mucus dehydration, resulting in reduced mucus clearance and airway mucus obstruction. The data provided here represents mRNA expression data from disseccted whole lung from male WT and Scnn1b-transgenic littermates (C57Bl/6NTac background) at 4 time points [postnatal days (PND) 0, 3, 10, and 42]. Histologically, PND 0 lungs are normal, at PND 3 the intrapulmonary airways exhibit transient and spotty Club cell necrosis, and by PND 10 airway mucus obstruction is evident in the proximal portion of the intrapulmonary main stem bronchus. At PND 42, Scnn1b-Tg lungs are charactyerized by chronic low level inflammation, with activated macrophages, neutrophilia, eosinophilia and increased incidence of bronchus-associated lymphoid tissue. The data from the WT mice provides a global look at mRNA post-natal developmental changes, while the data from the Scnn1b-transgenic line allows differential gene expression due to airway surface liquid dehydration and mucus obstruction to be queried.

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Saini Y, Dang H, Livraghi-Butrico A, Kelly EJ, Jones LC, O'Neal WK, Boucher RC