Postnatal requirement of the epithelial sodium channel for maintenance of epidermal barrier function.
In skin, the physiological consequence of an epithelial sodium channel (ENaC) deficiency is not obvious directly at birth. Nevertheless, within hours after birth, mice deficient for the alpha-subunit of the highly amiloride-sensitive epithelial sodium channel (alphaENaC/Scnn1a) suffer from a significant increased dehydration. This is characterized by a loss of body weight (by 6% in 6 h) and an increased transepidermal water loss, which is accompanied by a higher skin surface pH in 1-day-old pups. Although early and late differentiation markers, as well as tight junction protein distribution and function, seem unaffected, deficiency of alphaENaC severely disturbs the stratum corneum lipid composition with decreased ceramide and cholesterol levels, and increased pro-barrier lipids, whereas covalently bound lipids are drastically reduced. Ultrastructural analysis revealed morphological changes in the formation of intercellular lamellar lipids and the lamellar body secretion. Extracellular formation of the lamellar lipids proved to be abnormal in the knockouts. In conclusion, ENaC deficiency results in progressive dehydration and, consequently, weight loss due to severe impairment of lipid formation and secretion. Our data demonstrate that ENaC expression is required for the postnatal maintenance of the epidermal barrier function but not for its generation.
Département de Pharmacologie & de Toxicologie, Université de Lausanne, Rue du Bugnon 27, Lausanne, Switzerland.
Roch-Philippe
RP
Charles
Marjorie
M
Guitard
Céline
C
Leyvraz
Bernadette
B
Breiden
Marek
M
Haftek
Zofia
Z
Haftek-Terreau
Jean-Christophe
JC
Stehle
Konrad
K
Sandhoff
Edith
E
Hummler
D000222:Adaptation, Physiological; D000818:Animals; D000831:Animals, Newborn; D053503:Epithelial Sodium Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050356:Lipid Metabolism; D051379:Mice; D018345:Mice, Knockout; D010539:Permeability; D012867:Skin / Q000648:ultrastructure; D012879:Skin Physiological Phenomena; D019108:Tight Junctions / Q000502:physiology / Q000648:ultrastructure
D053503:Epithelial Sodium Channels; C507047:Scnn1a protein, mouse