ACTIVATION OF POLYAMINE CATABOLISM PROFOUNDLY ALTERS TISSUE POLYAMINEPOOLS AND AFFECTS HAIR-GROWTH AND FEMALE FERTILITY IN TRANSGENIC MICEOVEREXPRESSING SPERMIDINE SPERMINE N-1-ACETYLTRANSFERASE/

We have generated a transgenic mouse line that overexpresses the rate controlling enzyme of polyamine catabolism, spermidine/spermine N-1-ac etyltransferase. Tissues of these mice showed markedly distorted polya mine pools, which in most cases were characterized by the appearance o f N-1-acetylspermidine, not normally found in mouse tissues, a massive accumulation of putrescine, and decreases in spermidine and/or spermi ne pools. The most striking phenotypic change was permanent hair loss at the age of 3 to 4 weeks which was typified histologically by the ap pearance of extensive follicular cysts in the dermis, The effect seeme d attributable to putrescine interference with hair development, possi bly with differentiation/proliferation of epidermal cells located in h air follicles, Female members of the transgenic line were found to be infertile apparently due to ovarian hypofunction and hypoplastic uteri , The findings demonstrate the utility of spermidine/spermine N-1-acet yltransferase overexpression as an effective means for genetically mod ulating total tissue polyamine pools in transgenic animals and examini ng the developmental and oncogenic consequences.