Overexpression of Spermidine/Spermine N1-Acetyltransferase Under the Control of Mouse Metallothionein I Promoter in Transgenic Mice: Evidence for a Striking Post-Transcriptional Regulation of Transgene Expression by a Polyamine Analogue

The study involved generating a transgenic mouse line overexpressing the SSAT gene under a mouse metallothionein I promoter, leading to significant changes in tissue polyamine pools and delayed permanent hair loss compared to previous models. The liver was notably affected, with drastic reductions in spermine and increases in putrescine. Despite high levels of SSAT mRNA, enzyme activity was only moderately elevated unless induced by ZnSO4 or the polyamine analogue DENSPM, which caused a massive increase in enzyme activity and depletion of spermidine and spermine pools. This treatment led to high mortality and liver damage, indicating that SSAT overexpression made the mice highly sensitive to polyamine analogues, suggesting a post-transcriptional regulation mechanism.