TRANSGENIC MICE OVEREXPRESSING ORNITHINE AND S-ADENOSYLMETHIONINE DECARBOXYLASES MAINTAIN A PHYSIOLOGICAL POLYAMINE HOMEOSTASIS IN THEIR TISSUES

Recent work has shown that transgenic mice overexpressing human ornith ine decarboxylase display no marked changes in the tissue concentratio ns of spermidine or spermine in spite of a dramatic increase in putres cine levels. In the tissues of transgenic mice carrying the human sper midine synthase gene and in those of hybrid mice overexpressing both o rnithine decarboxylase and spermidine synthase, spermidine and spermin e levels remain within normal limits. To test whether the amount of th e propylamine group donor, decarboxylated S-adenosylmethionine, limits the conversion of putrescine into the higher polyamines, we have prod uced transgenic mouse lines harbouring the rat S-adenosylmethionine de carboxylase gene in their genome. However, neither these mice nor the hybrid mice overexpressing both ornithine decarboxylase and S-adenosyl methionine decarboxylase displayed significant changes in their spermi dine and spermine tissue levels. To study the mechanism by which cells maintain the constancy of the polyamine concentrations, we have deter mined the metabolic flux of polyamines in transgenic primary fibroblas ts using pulse labelling. The results indicate that the polyamine Bow is faster in transgenic primary fibroblasts than in non-transgenic fib roblasts and that the intracellular homoeostasis of higher polyamines is maintained at least partly by the acetylation of spermidine and spe rmine and their secretion into the medium.