title: Basal transepidermal water loss is increased in platelet-type 12-lipoxygenase deficient mice.
abstract: The roles of fatty acids in the skin have been under investigation since early reports of the phenotypic abnormalities of mice fed a diet deficient in essential fatty acids. Little is known about the functional significance of fatty acid metabolism by lipoxygenases in epidermis. Here, we have examined the role of platelet-type 12-lipoxygenase which converts arachidonic acid to the oxygenated metabolite 12-hydroperoxyeicosatetraenoic acid, in the skin using platelet-type 12-lipoxygenase-deficient mice generated by gene targeting. Platelet-type 12-lipoxygenase in wild-type mice was localized to the stratum granulosum by immunohistochemical analysis. Platelet-type 12-lipoxygenase-deficient mice lacked immunodetectable platelet-type 12-lipoxygenase in platelets and epidermis, appeared grossly normal, and exhibited an increase in basal transepidermal water loss without alteration in basal mitotic activity. Water loss and mitotic activity in mice with an acetone-disrupted membrane barrier were normal. No defect in ultrastructural properties or content of major fatty acids in dorsal skin or ear inflammation response was apparent in platelet-type 12-lipoxygenase-deficient mice. These results indicate that the platelet-type 12-lipoxygenase pathway in mice is partly responsible for normal permeability barrier function but the mechanism awaits further elucidation.
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: E N
authors.initials: EN
authors.lastname: Johnson
authors.forename: L B
authors.initials: LB
authors.lastname: Nanney
authors.forename: J
authors.initials: J
authors.lastname: Virmani
authors.forename: J A
authors.initials: JA
authors.lastname: Lawson
authors.forename: C D
authors.initials: CD
authors.lastname: Funk
mesh_terms: D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000172:deficiency*; D001095:Arachidonic Acids / Q000009:adverse effects / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology*; D003877:Dermatitis, Contact / Q000209:etiology; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains / Q000502:physiology*; D008854:Microscopy, Electron; D008940:Mitotic Index; D014870:Water Loss, Insensible / Q000502:physiology*
chemical_list: D001095:Arachidonic Acids; D001092:Arachidonate 12-Lipoxygenase