Downregulation of Ke 6, a novel gene encoded within the major histocompatibility complex, in murine polycystic kidney disease.

Abstract

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/tw5 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 possess 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.

Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease

“…This area is well known to contain genes encoding the human major histocompatibility complex (MHC). This complex is thought to be involved in polycystic kidney disease (PKD) since aberrant expression has been found in two different models of PKD mice (Aziz et al 1993). Recently, Fomitcheva et al (1998) have found that the overexpressed protein fused with GST catalyzes efficiently the transformation of E 2 to E 1 .…”

The Prostate Expression Database (PEDB)

“…For example, germline mutations in 173-HSD 3 and 4 result in the male pseudohermaphroditism (Geissler et al, 1994) and the fatal form of Zellweger syndrome (de Launoit and Adamski, 1999; Peltoketo et al, 1999), respectively. Abnormal regulation of 17p-HSD8 {Ke 6), an alternatively spliced gene member of the SDR family, has been linked to recessive polycystic kidney disease in mice (Aziz et al, 1993). Allelic variants in the 3p-HSD 2 gene, encoding one of two enzymes that initiates the inactivation of dihydrotestosterone, have been identified and are currently under assessment for a role in racial/ethnic differences in prostate carcinogenesis (Devgan et al, 1997).…”

Ke 6 Gene

“…We reported the identification of a new mammalian gene, Ke 6, whose expression is specifically repressed in two different murine models of PKD: the cpk and jck mouse (7). The Ke 6 gene is encoded within the major histocompatibility complex and is a member of the superfamily of short-chain alcohol dehydrogenases.…”

“…The Ke 6 gene is encoded within the major histocompatibility complex and is a member of the superfamily of short-chain alcohol dehydrogenases. The normal expression pattern of the Ke 6 gene is very high in kidney and liver (7), the two organs that are most extensively affected in polycystic kidney disease. We have postulated that the Ke 6 gene may encode steroid dehydrogenase activity, since it has substantial homology to specific functional domains of bacterial and mammalian steroid dehydrogenases (8).…”