title: Early death due to defective neonatal lung liquid clearance in alpha-ENaC-deficient mice.
abstract: The amiloride-sensitive epithelial sodium channel, ENaC, is a heteromultimeric protein made up of three homologous subunits (alpha, beta and gamma) (1,2). In vitro, assembly and expression of functional active sodium channels in the Xenopus oocyte is strictly dependent on alpha-ENaC--the beta and gamma subunits by themselves are unable to induce an amiloride-sensitive sodium current in this heterologous expression system (2). In vivo, ENaC constitutes the limiting step for sodium absorption in epithelial cells that line the distal renal tubule, distal colon and the duct of several exocrine glands. The adult lung expresses alpha, beta and gamma ENaC (3,4), and an amiloride-sensitive electrogenic sodium reabsorption has been documented in upper and lower airways (3-7), but it is not established whether this sodium transport is mediated by ENaC in vivo. We inactivated the mouse alpha-ENaC gene by gene targeting. Amiloride-sensitive electrogenic Na+ transport was abolished in airway epithelia from alpha-ENaC(-/-) mice. Alpha-ENaC(-/-) neonates developed respiratory distress and died within 40 h of birth from failure to clear their lungs of liquid. This study shows that ENaC plays a critical role in the adaptation of the newborn lung to air breathing.
authors.affiliation: Institut de Pharmacologie et de Toxicologie de l'Université, Lausanne, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Hummler
authors.forename: P
authors.initials: P
authors.lastname: Barker
authors.forename: J
authors.initials: J
authors.lastname: Gatzy
authors.forename: F
authors.initials: F
authors.lastname: Beermann
authors.forename: C
authors.initials: C
authors.lastname: Verdumo
authors.forename: A
authors.initials: A
authors.lastname: Schmidt
authors.forename: R
authors.initials: R
authors.lastname: Boucher
authors.forename: B C
authors.initials: BC
authors.lastname: Rossier
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001826:Body Fluids / Q000378:metabolism; D046508:Culture Techniques; D017931:DNA Primers; D053503:Epithelial Sodium Channels; D018390:Gene Targeting; D017136:Ion Transport; D008171:Lung Diseases / Q000378:metabolism* / Q000401:mortality; D051379:Mice; D008969:Molecular Sequence Data; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D017931:DNA Primers; D053503:Epithelial Sodium Channels; D015222:Sodium Channels; D012964:Sodium