ISOLATION OF THE MOUSE ALDOSE REDUCTASE PROMOTER AND IDENTIFICATION OF A TONICITY-RESPONSIVE ELEMENT

Aldose reductase (AR; EC 1.1.1.21) is an oxidoreductase that catalyzes the NADPH-dependent conversion of glucose to sorbitol, the first step of the polyol pathway. AR is of great interest due to its implication in the etiology of diabetic complications. In renal medullary cells, AR also plays an osmoregulatory role by accumulating sorbitol to maint ain the intracellular osmotic balance during antidiuresis. We have pre viously cloned the AR cDNA from mouse kidney, and we report here the i solation of the mouse AR gene promoter. Transient transfection of chlo ramphenicol acetyltransferase reporter constructs containing various 5 '-flanking regions of the mouse AR gene in CV1 cells led to the identi fication of a sequence spanning base pairs -1053 to -1040, required fo r an enhancer activity in hypertonic compared with isotonic cell cultu re conditions. This sequence is similar to the tonicity-responsive ele ment first characterized in the betaine-gamma-aminobutyric acid transp orter promoter.