Studies on the mechanism of tissue-specific gene expression by the use of transgenic mice.

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In vertebrates, pigmentation is observed mainly in skin and eyes where pigment cells exist. This tissue-specific melanogenesis is considered to involve cell type specific expression of the tyrosinase gene. In mice, it is known that tyrosinase is encoded at the c-locus on chromosome 7 and that deficiency of the gene results in an amelanotic phenotype. We have shown that sequences in the 2.6-kb 5' upstream region of the mouse tyrosinase gene are responsible for cell type-specific expression of the mouse tyrosinase cDNA in the transgenic mice.An attempt was made to find any element that is involved in the cell type-specific expression in other mammals. In the present experiment, we constructed a fused gene which contains the 1.0-kb 5' flanking sequence of the human tyrosinase gene ligated with the mouse tyrosinase cDNA. By introducing the fused gene into fertilized eggs of albino mice, we obtained transgenic pigmented mice and analyzed the expression pattern of the transgene. We obtained two mice that exhibited pigmentation in the skin and eyes, and established a transgenic lines from one of them. In the animals of the line, melanogenesis was found only in eyes and hair follicles though the transgenes were found integrated in all tissues examined. Therefore, it seems that the 1.0-kb 5' upstream region of the human tyrosinase gene contains conserved cis-elements essential for cell type-specific expression of the genes in mice and humans. In some tissues, however, tyrosinase activity and tyrosinase mRNA were detected. It seems possible that a cell type-specific post-transcriptional regulation mechanism is present in the mouse cells.