A mouse organotypic tissue culture model for autosomal recessive congenital ichthyosis
A mouse organotypic tissue culture model for autosomal recessive congenital ichthyosis
复制标题
常染色体隐性遗传先天性鱼鳞病小鼠器官组织培养模型
DOI：
10.1111/bjd.13308
复制
发表时间：
2014
影响因子：
10.3
通讯作者：
Schneider
中科院分区：
文献类型：
--
作者：
Rosenberger;Latzko;Hausser;Schneider
研究背景常染色体隐性遗传性先天性鱼鳞病（autosomalrecessivecongenitalichthyoses，ARCIs）是一种由皮肤屏障功能受损引起的皮肤角化疾病.编码脂氧合酶12 R-LOX和eLOX-3的基因突变是ARCIs的第二大常见原因。近年来，人类皮肤等价物recapituting的ARCI phenotype.ObjectivesTo开发一个小鼠器官型组织培养模型ARCI.MethodsEpidermal角质形成细胞分离自新生儿12 R-LOX-缺陷小鼠和小鼠真皮成纤维细胞包埋在天然胶原蛋白I型支架共培养。所有的表皮层都存在，并且其中的角质形成细胞显示出特征性的形态特征。分化和成熟的标志物表明规则的表皮形态发生。表皮结构的主要成分得到表达，并且明显地被适当地加工和组装。与其野生型对应物相比，12 R-LOX-缺陷皮肤等同物在上表皮层中显示出异常的囊泡结构，与脂质组成改变和经表皮水分损失增加相关，与12 R-LOX-缺陷小鼠相当。将它们分类为适当的体外模型，以研究ARCI发展的分子机制并评估新的治疗药物。与现有的人类三维皮肤模型相比，这些小鼠模型的生成不受有限材料供应的限制，并且不依赖于可能导致无意的基因型和表型改变的体外扩增和/或遗传操作。
BackgroundAutosomal 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.ObjectivesTo develop a murine organotypic tissue culture model for ARCI.MethodsEpidermal keratinocytes were isolated from newborn 12R‐LOX‐deficient mice and cocultivated with mouse dermal fibroblasts embedded in a scaffold of native collagen type I.ResultsWith this experimental set‐up the keratinocytes formed a well‐organized multilayered stratified epithelium resembling skin architecturein vivo. 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.ConclusionsThe mouse skin equivalents faithfully recapitulate the 12R‐LOX‐deficient phenotype observedin vivo, classifying them as appropriatein vitromodels 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 onin vitroexpansion and/or genetic manipulations that could result in inadvertent genotypic and phenotypic alterations.
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影响因子：
3.9
作者：
Eckl, KM;Krieg, P;Hennies, HC
通讯作者：
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DOI：
--
发表时间：
2009
期刊：
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作者：
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作者：
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通讯作者：
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影响因子：
4.4
作者：
A. Kinzig;M. Heidt;Gerhard Fürstenberger;Friedrich Marks;P. Krieg
通讯作者：
P. Krieg
DOI：
10.1016/j.bbalip.2013.08.020
发表时间：
2014-03
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Muñoz-Garcia A;Thomas CP;Keeney DS;Zheng Y;Brash AR
通讯作者：
Brash AR