Expression of tyrosinase gene in transgenic mice: programmed versus non-programmed expression.

The transgenic experiment is a useful tool for the study of cell type-specific expression of genes during embryogenesis. We constructed a minigene, mg-Tyrs-J, by fusing a tyrosinase cDNA, Tyrs-J, with the 5' upstream region of genomic deoxyribonucleic acid (DNA) clone, G3L, and microinjected this minigene into fertilized eggs from albino BALB/c mice. It was expected that a melanin pigment would be produced and deposited in the melanosomes of melanocytes of BALB/c mice if the mg-Tyrs-J was expressed in a cell type-specific manner. In the transgenic mice, melanin pigments were observed only in melanocytes and in hair shafts of hair follicles, and in the choroid and pigmented epithelium of the eyes. However, Southern blot analysis of the genomic DNA of the transgenic mice showed that the transgene was present in all tissues examined. These results apparently indicate that the introduced transgene is integrated into a chromosome(s) and distributed among somatic cells, whereas the gene is expressed exclusively in melanocytes, i.e., the transgene is expressed in a cell type-specific manner. Some founder mice were crossed with BALB/c albino mice to establish transgenic lines. Each line and subline shows inherited characteristic phenotypes; in particular, offsprings from two founders exhibited a patched phenotype. The possible mechanism of this interesting expression of these transgenes is discussed in comparison with the results of other investigators who observed both programmed and non-programmed expression of the tyrosinase gene in transgenic mice.