Characterization of genomic regions directing the cell-specific expression of the mouse aldose reductase gene.

Aldose reductase (AR), an enzyme implicated in the pathogenesis of diabetic complications, is highly expressed in such target organs of complications as the lens and peripheral nerve of experimental animals. In mouse, however, a very low level of the transcript was expressed in these tissues. To explore the unique expression pattern of AR in mice, genomic structure and upstream regions regulating the basal expression of the enzyme were determined. In NIH3T3 cells, a -1.1-kb upstream portion demonstrated the highest promoter activity. The ability to drive the luciferase reporter gene was reduced by 56% when the -1.1/-0.86-kb region was deleted. In Chinese hamster ovary (CHO) cells, deletion up to -0.67 kb did not affect basal promoter activity. The activity in CHO cells was reduced by 73% when the -0. 67/-0.24-kb region was deleted. These findings indicate that a genomic region directing the cell-specific transcription of the mouse AR gene exists. Copyright 1999 Academic Press.