Syastematic isolation and characterization of genes involved in morphogenesis of skin and their relevance to human skin diseases.

为了更好地了解表皮细胞的正常生长和分化以及恶性转化，系统地分离和鉴定相关基因至关重要。为此，我们利用小鼠表皮结构的特征性发育变化，即，在13.5 dpc时，表皮的简单基底层通过增加更多的分化层而逐渐分层，导致在16.5 dpc时完全复层的皮质上皮。利用12.5 ~ 16.5dpc的表皮RNA进行RNA微阵列显示，分离到7个未知基因。在迄今为止所表征的那些中，从序列同源性和特征性氨基酸重复推断，命名为4C 32的一个为角蛋白相关蛋白。另一个基因4A 40是一个大的转录本（>10 kb），含有重复的氨基酸序列和间隔区，可能以类似于聚丝蛋白原的方式进行蛋白水解加工。4A 50基因与人不育相关蛋白75 kDa具有同源性，且随着睾丸发育成熟，其表达量逐渐增加。目前的研究结果表明，我们的方法是适合系统地分离基因参与皮肤的生长/分化，和分离的基因的表征将提供有趣的信息，皮肤生物学和肿瘤学。

For the better understanding of normal growth and differentiation as well as malignant conversion of epidermal cells, it is critically important to systematically isolate and characteriza involved genes. For this purpose, we utilized characteistic developmental change of mouse epidermal architecture, i.e., the simple basal layer of epidermis at 13.5 dpc stratifies progressively by the addition of more differentiated layers, resulting in a fully differetiated cornified epithelium at 16.5 dpc. By RNA differetial display using epidermal RNA from 12.5 dpc to 16.5 dpc, seven yet unknown genes were isolated. Among those characterized until now, one designated as 4C32 was deduced as a keratin-associated protein from the sequence homology and characteristic amino acid repeats. Another gene, 4A40, was a large transcript (>10 kb) and contained repetitive amino acid sequences with spacer, possibly processed proteolytically in a similar way as profilaggrin. A gene designated as 4A50 showed sequence homology with human infertility-related 75 kDa protein, and its expressio level actually increased with the maturation of testis. The present results indicate that our approach is suitable to systematically isolate genes involved in growth/differentiation of skin, and that characterization of the isolated genes will provide intriguing information on skin biology and oncology.