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

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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.