Aloxe3 knockout mice reveal a function of epidermal lipoxygenase-3 as hepoxilin synthase and its pivotal role in barrier formation
Krieg P, Rosenberger S, De Juanes S, Latzko S, Hou J, Dick A, Kloz U, Van Der Hoeven F, Hausser I, Esposito I, Rauh M, Schneider H (2013)
Publication Type: Journal article
Publication year: 2013
Journal
Book Volume: 133
Pages Range: 172-180
Journal Issue: 1
DOI: 10.1038/jid.2012.250
Abstract
Loss-of-function mutations in the lipoxygenase (LOX) genes ALOX12B and ALOXE3 are the second most common cause of autosomal recessive congenital ichthyosis. The encoded proteins, 12R-LOX and epidermal LOX-3 (eLOX-3), act in sequence to convert fatty acid substrates via R-hydroperoxides to specific epoxyalcohol derivatives and have been proposed to operate in the same metabolic pathway during epidermal barrier formation. Here, we show that eLOX-3 deficiency in mice results in early postnatal death, associated with similar but somewhat less severe barrier defects and morphological changes than reported earlier for the 12R-LOX-knockout mice. Skin lipid analysis demonstrated that the severity of barrier failure is related to the loss of covalently bound ceramides in both 12R-LOX- and eLOX-3-null mice, confirming a proposed functional linkage of the LOX pathway to ceramide processing and formation of the corneocyte lipid envelope. Furthermore, analysis of free oxygenated fatty acid metabolites revealed strongly reduced levels of hepoxilin metabolites in eLOX-3-deficient epidermis, indicating an additional function of eLOX-3 in mammalian skin as a hepoxilin synthase linked to the 12S-LOX pathway. © 2013 The Society for Investigative Dermatology.
Authors with CRIS profile
Manfred Rauh
Department of Paediatrics and Adolescent Medicine
Holm Schneider
Professur für Kinderheilkunde/Experimentelle Perinatalmedizin
Involved external institutions
Deutsches Krebsforschungszentrum (DKFZ)
Germany (DE)
Universitätsklinikum Heidelberg
Germany (DE)
Technische Universität München (TUM)
Germany (DE)
Germany (DE)
Universitätsklinikum Heidelberg
Germany (DE)
Technische Universität München (TUM)
Germany (DE)
How to cite
APA:
Krieg, P., Rosenberger, S., De Juanes, S., Latzko, S., Hou, J., Dick, A.,... Schneider, H. (2013). Aloxe3 knockout mice reveal a function of epidermal lipoxygenase-3 as hepoxilin synthase and its pivotal role in barrier formation. Journal of Investigative Dermatology, 133(1), 172-180. https://doi.org/10.1038/jid.2012.250
MLA:
Krieg, Peter, et al. "Aloxe3 knockout mice reveal a function of epidermal lipoxygenase-3 as hepoxilin synthase and its pivotal role in barrier formation." Journal of Investigative Dermatology 133.1 (2013): 172-180.
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