PRESENCE OF A CLOSELY-RELATED SUBGROUP IN THE ALDO-KETOREDUCTASE FAMILY OF THE MOUSE

Aldose reductase (alditol:NAD(P)(+) 1-oxidoreductase), an enzyme implicated in the pathogenesis of various diabetic complications, catalyzes the reduction of a variety of aldehydes. From a mouse kidney library, we isolated aldose reductase cDNA that encodes a 316-amino-acid protein with approximately 97 % identity to rat lens aldose reductase, approximately 69 % identity to the mouse vas deferens protein and also approximately 69 % identity to mouse fibroblast growth-factor-l-regulated protein. RNA-blot analysis demonstrated abundant expression of the enzyme transcript in the testis, skeletal muscle and kidney. However, a very low level of the transcript was detected in the sciatic nerve and lens, where abundant expression and involvement of the enzyme in diabetic complications were documented in other animals species. The isolated cDNA was expressed in Escherichia coli and the recombinant protein was purified to homogeneity by affinity chromatography and chromatofocusing. The expressed enzyme demonstrated reductase activity for various aldo sugars but not for the steroids. The enzyme reaction with DL-glyceraldehyde was, however, competitively inhibited by progesterone or 17 alpha-hydroxyprogesterone. The results not only indicate a unique tissue distribution and enzyme attribute of mouse aldose reductase, but also the presence of a closely related subgroup within the aldo-oxidoreductase superfamily in mouse tissues.