ABNORMAL REGULATION OF THE KE-6 GENE, A NEW 17-BETA-HYDROXYSTEROID-DEHYDROGENASE IN THE CPK MOUSE KIDNEY

The function encoded by the Ke 6 gene has been recently determined to be 17 beta-hydroxysteroid dehydrogenase. Previously, the abnormal expr ession of the Ke 6 gene has been intimately associated with developmen t of recessive polycystic kidney disease. The Ke 6 gene is normally ex pressed at very high levels in the kidney and liver and is severely do wn regulated in all recessive murine models of polycystic kidney disea se that have been examined to date. Here, we report a detailed examina tion of the promoter region of the Ke 6 gene in normal mouse kidney ce lls (CTA) and in cells derived from mouse kidneys homozygous for the c pk (congenital polycystic kidney) mutation, using transfection analysi s and DNA-protein gel shift assays. The minimal promoter region, P1 (1 to -96), and a putative enhancer site, P3 (-165 to -256), within the Ke 6 gene 5' flanking sequence have been identified. We have also ide ntified another region, P2 (-97 to -165), that may be responsible for the lower promoter activity of the Ke 6 gene in cpk cells. Furthermore , absence of binding of a 38 kDa nuclear protein to a 16 bp sequence e lement (P1A) within the minimal promoter of the Ke 6 gene suggests tha t the P1A element could be responsible for the overall reduction in pr omoter function in cpk cells. (C) 1998 Elsevier Science Ireland Ltd. A ll rights reserved.