Characterization of genomic regions directing the cell-specific expressionof 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 exp lore the unique expression pattern of AR in mice, genomic structure and ups tream regions regulating the basal expression of the enzyme were determined . In NIH3T3 cells, a -1.1-kb upstream portion demonstrated the highest prom oter activity. The ability to drive the luciferase reporter gene was reduce d by 56% when the -1.1/-0.86-kb region was deleted. In Chinese hamster ovar y (CHO) cells, deletion up to -0.67 kb did not affect basal promoter activi ty. The activity in CHO cells was reduced by 73% when the -0.67/-0.24-kb re gion was deleted. These findings indicate that a genomic region directing t he cell-specific transcription of the mouse AR gene exists. (C) 1999 Academ ic Press.