REGULATION OF THE EXPRESSION OF HUMAN ORNITHINE DECARBOXYLASE GENE AND ORNITHINE DECARBOXYLASE PROMOTER-DRIVEN REPORTER GENE IN TRANSGENIC MICE

We have studied the regulation of the expression of ornithine decarbox ylase with the aid of transgenic mice harbouring either functional hum an ornithine decarboxylase genes or the mouse ornithine decarboxylase promoter-driven chloramphenicol acetyltransferase fusion gene in their genome. We used three different stimuli which are well known to enhan ce ornithine decarboxylase activity in their appropriate target tissue s: (i) testosterone in female kidney, (ii) a phorbol ester in epidermi s and (iii) partial hepatectomy in liver. Endogenous mouse ornithine d ecarboxylase activity was strikingly stimulated in response to these t reatments. Even though containing the 5' flanking region of the mouse ornithine decarboxylase gene, known to possess full promoter activity, the chloramphenicol acetyltransferase reporter gene was entirely inse nsitive to any of these stimuli. The human transgene-derived ornithine decarboxylase activity in kidney was unaffected by testosterone treat ment. but responded in skin to application of the phorbol ester and li kewise was clearly enhanced in regenerating liver. Although mouse endo genous ornithine decarboxylase mRNA levels were distinctly elevated af ter testosterone, this treatment did not influence the accumulation of the human transgene-derived mRNA. The phorbol ester enhanced the accu mulation of mouse endogenous ornithine decarboxylase mRNA and also tha t derived from the human transgene; however, the enzyme activity was s timulated in regenerating liver without appreciable changes in the lev els of endogenous or transgene-derived message. Our present results st rongly emphasize the central role of the coding sequence of ornithine decarboxylase gene in the induction of the enzyme activity.