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The Lankenau Medical Research Center, Wynnewood, Pennsylvania 19096 [L. M., S. K. G., D. R., A. P. S., J. A. S., T. G. O.], and I. Medical Department, Johannes-Gutenberg University, Mainz, Germany [M. B.]
Ornithine decarboxylase, a critical regulatory enzyme for polyamine biosynthesis, is highly inducible by growth-promoting stimuli in mouse epidermis but the enzyme level is only transiently elevated due to rapid turnover of the protein. Here we report that constitutive overexpression of the enzyme in the skin of transgenic mice causes several phenotypic abnormalities. Effects observed include development of dermal follicular cysts, excessive skin wrinkling, enhanced nail growth, alopecia, and spontaneous tumor development. These results indicate that up-regulation of polyamine biosynthesis can profoundly disturb skin homeostasis and alter susceptibility to neoplastic development.
1 This work was supported by NIH Grant ES01664 (T.G.O.). S.K.G. was also supported by NIH Grant CA55066 and an American Cancer Society Junior Faculty Research Award. M.B. is supported by the Boehringer Ingelheim Foundation.
2 To whom requests for reprints should be addressed, at The Lankenau Medical Research Center, 100 Lancaster Avenue, Wynnewood, PA 19096.
Received 6/30/95. Accepted 8/18/95.
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