INCREASED FREQUENCY OF SPONTANEOUS SKIN TUMORS IN TRANSGENIC MICE WHICH OVEREXPRESS ORNITHINE DECARBOXYLASE

Ornithine decarboxylase, a critical regulatory enzyme for polyamine bi osynthesis, is highly inducible by growth-promoting stimuli in mouse e pidermis but the enzyme level is only transiently elevated due to rapi d turnover of the protein, Here we report that constitutive overexpres sion of the enzyme in the skin of transgenic mice causes several pheno typic abnormalities. Effects observed include development of dermal fo llicular cysts, excessive skin wrinkling, enhanced nail growth, alopec ia, and spontaneous tumor development. These results indicate that up- regulation of polyamine biosynthesis can profoundly disturb skin homeo stasis and alter susceptibility to neoplastic development.