Lung disease phenotypes caused by overexpression of combinations of α-, β-, and γ-subunits of the epithelial sodium channel in mouse airways

American Journal of Physiology. Lung Cellular and Molecular Physiology
Alessandra Livraghi-ButricoBarbara R Grubb

Abstract

The epithelial Na+ channel (ENaC) regulates airway surface hydration. In mouse airways, ENaC is composed of three subunits, α, β, and γ, which are differentially expressed (α > β > γ). Airway-targeted overexpression of the β subunit results in Na+ hyperabsorption, causing airway surface dehydration, hyperconcentrated mucus with delayed clearance, lung inflammation, and perinatal mortality. Notably, mice overexpressing the α- or γ-subunit do not exhibit airway Na+ hyperabsorption or lung pathology. To test whether overexpression of multiple ENaC subunits produced Na+ transport and disease severity exceeding that of βENaC-Tg mice, we generated double (αβ, αγ, βγ) and triple (αβγ) transgenic mice and characterized their lung phenotypes. Double αγENaC-Tg mice were indistinguishable from WT littermates. In contrast, double βγENaC-Tg mice exhibited airway Na+ absorption greater than that of βENaC-Tg mice, which was paralleled by worse survival, decreased mucociliary clearance, and more severe lung pathology. Double αβENaC-Tg mice exhibited Na+ transport rates comparable to those of βENaC-Tg littermates. However, αβENaC-Tg mice had poorer survival and developed severe parenchymal consolidation. In situ hybridization (RNAscope) analysi...Continue Reading

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Feb 5, 2013·American Journal of Physiology. Lung Cellular and Molecular Physiology·Alessandra Livraghi-ButricoBarbara R Grubb
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Jan 23, 2015·Chest·Charles R EstherRichard C Boucher

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Citations

Jul 3, 2021·International Journal of Molecular Sciences·Dominik H W LeitzMarcus A Mall
May 27, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Arun K RoojBakhrom K Berdiev

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Methods Mentioned

BETA
transgenic
bronchoalveolar lavage
lavage
electrophoresis
Infrared Imaging
genotyping
bronchoalveolar

Software Mentioned

R package

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