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
References
Oct 1, 1993·The American Journal of Physiology·T C ChinetM J Stutts
Nov 20, 1997·The Journal of Clinical Investigation·M R KnowlesR C Boucher
Jul 3, 1998·The Journal of Clinical Investigation·M MallK Kunzelmann
Apr 13, 2004·Nature Medicine·Marcus MallRichard C Boucher
Oct 7, 2004·The Journal of Biological Chemistry·Rebecca P HugheyThomas R Kleyman
Jun 15, 2007·The Journal of General Physiology·Arun Anantharam, Lawrence G Palmer
Jul 7, 2007·The Journal of Biological Chemistry·Robert H MeltzerDale J Benos
Feb 9, 2008·The Journal of Physiology·Yunxiang ZhuC William Davis
Mar 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alessandra LivraghiScott H Randell
Dec 15, 2010·The Journal of Biological Chemistry·Daniel M Collier, Peter M Snyder
Jul 22, 2011·The Journal of Biological Chemistry·Andrew P StewartJ Michael Edwardson
Sep 18, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Hong-Long JiSadis Matalon
Feb 5, 2013·American Journal of Physiology. Lung Cellular and Molecular Physiology·Alessandra Livraghi-ButricoBarbara R Grubb
Jul 24, 2013·The Journal of Physiology·Carey A HobbsRobert Tarran
Apr 1, 2014·American Journal of Respiratory and Critical Care Medicine·Stefanie GehrigMarcus A Mall
Jan 23, 2015·Chest·Charles R EstherRichard C Boucher
Citations
Feb 8, 2018·Translational Oncology·Min HeMelanie H Cobb
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