DOWN-REGULATION OF KE-6, A NOVEL GENE ENCODED WITHIN THE MAJOR HISTOCOMPATIBILITY COMPLEX, IN MURINE POLYCYSTIC KIDNEY-DISEASE

Polycystic kidney disease (PKD) is characterized by progressive enlargement of the kidneys due to numerous expanding cysts ultimately leading to renal failure. We have identified a gene, Ke 6, located within the H-2K/t(w5) region on mouse chromosome 17, which is downregulated in two distinct murine models of heritable PKD. Ke 6 is a member of the short-chain alcohol dehydrogenase family and possesses remarkable amino acid sequence conservation with several bacterial proteins with oxidoreductase function. The Ke 6 gene gives rise to two transcripts-a 1-kb Ke 6a mRNA which is abundant in kidney and liver tissue and a 1.4-kb Ke 6b mRNA which is found at a moderate level in spleen tissue. We report here the complete nucleotide sequence of Ke 6a cDNA and the expression of the Ke 6 gene in murine models of PKD. The Ke 6 gene may be intimately involved in the manifestation of these cystic kidney diseases.