A mouse organotypic tissue culture model for autosomal recessive congenital ichthyosis. (13th November 2014)

• Record Type: Journal Article
• Authors: Rosenberger, S.; Dick, A.; Latzko, S.; Hausser, I.; Stark, H.‐J.; Rauh, M.; Schneider, H.; Krieg, P.
• Is Part Of: British journal of dermatology. Volume 171:Number 6(2014:Dec.)
• Page Start: 1347
• Page End: 1357
• Publication Date: 2014-11-13
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.13308
• Languages: English
• ISSNs: 0007-0963

Abstract

<abstract abstract-type="main" id="bjd13308-abs-0001"> <title>Summary</title> <sec id="bjd13308-sec-0001" sec-type="section"> <title>Background</title> <p>Autosomal recessive congenital ichthyoses (ARCIs) are keratinization disorders caused by impaired skin barrier function. Mutations in the genes encoding the lipoxygenases 12R‐LOX and eLOX‐3 are the second most common cause of ARCIs. In recent years, human skin equivalents recapitulating the ARCI phenotype have been established.</p> </sec> <sec id="bjd13308-sec-0002" sec-type="section"> <title>Objectives</title> <p>To develop a murine organotypic tissue culture model for ARCI.</p> </sec> <sec id="bjd13308-sec-0003" sec-type="section"> <title>Methods</title> <p>Epidermal keratinocytes were isolated from newborn 12R‐LOX‐deficient mice and cocultivated with mouse dermal fibroblasts embedded in a scaffold of native collagen type I.</p> </sec> <sec id="bjd13308-sec-0004" sec-type="section"> <title>Results</title> <p>With this experimental set‐up the keratinocytes formed a well‐organized multilayered stratified epithelium resembling skin architecture <italic>in vivo</italic>. All epidermal layers were present and the keratinocytes within showed the characteristic morphological features. Markers for differentiation and maturation indicated regular epidermal morphogenesis. The major components of epidermal structures were expressed, and were obviously processed and assembled properly. In contrast to their wild‐type counterparts, 12R‐LOX‐deficient skin equivalents showed abnormal vesicular structures in the upper epidermal layers correlating with altered lipid composition and increased transepidermal water loss, comparable with 12R‐LOX‐deficient mice.</p> </sec> <sec id="bjd13308-sec-0005" sec-type="section"> <title>Conclusions</title> <p>The mouse skin equivalents faithfully recapitulate the 12R‐LOX‐deficient phenotype observed <italic>in vivo</italic>, classifying them as appropriate <italic>in vitro</italic> models to study molecular mechanisms involved in the development of ARCI and to evaluate novel therapeutic agents. In contrast to existing human three‐dimensional skin models, the generation of these murine models is not constrained by a limited supply of material and does not depend on <italic>in vitro</italic> expansion and/or genetic manipulations that could result in inadvertent genotypic and phenotypic alterations.</p> </sec> </abstract>