TRANSGENIC MICE EXPRESSING THE HUMAN ORNITHINE DECARBOXYLASE GENE UNDER THE CONTROL OF MOUSE METALLOTHIONEIN-I PROMOTER

We have generated a transgenic mouse line harbouring the human ornithi ne decarboxylase gene under the control of mouse metallothionein I pro moter. Even in the absence of an exposure to heavy metals, ornithine d ecarboxylase was over-expressed in heart, testis, brain, and especiall y in liver, of the transgenic animals. An exposure of the transgenic m ice to zinc further enhanced the enzyme activity to a level which in l iver represented up to 8000-fold increase in comparison with non-trans genic animals. The striking stimulation of liver ornithine decarboxyla se activity upon treatment of the transgenic mice with zinc was accomp anied by a nearly 150-fold increase in the hepatic putrescine content as compared with similarly treated nontransgenic animals. Even though the liver putrescine concentration reached that of spermidine and sper mine in the transgenic animals, the contents of the higher polyamines only transiently increased upon zinc administration and then returned to the basal level.:These findings once again indicate that mammalian cells possess extremely powerful regulatory machinery to prevent an ov er-accumulation of spermidine and spermine in nondividing cells, and t hat very high tissue putrescine concentrations can be tolerated, at le ast for periods of a few days, with seemingly no phenotypic changes.