Ke 6 Gene: SEQUENCE AND ORGANIZATION AND ABERRANT REGULATION IN MURINE POLYCYSTIC KIDNEY DISEASE

Michele M Maxwell,Jacqueline Nearing,Nazneen Aziz

doi:10.1074/jbc.270.42.25213

Abstract

Ke 6 gene is a newly identified gene located in the major histocompatibility complex and is a candidate steroid dehydrogenase gene because of structural homology and regulatory similarities with mammalian steroid dehydrogenases. We report here the complete nucleotide sequence and intron-exon organization of the Ke 6 gene and cloning of the alternatively spliced Ke 6b transcript. We find that Ke 6 gene expression is down-regulated in pcy mice which is a murine model of polycystic kidney disease (PKD). Thus far, Ke 6 gene expression is down-regulated in all murine models of PKD we have examined. Abnormal steroid metabolism as a possible cause of PKD is discussed.

Highlights

Polycystic kidney disease (PKD)1 is a major inherited cause of renal failure in humans
We reported the identification of a new mammalian gene, Ke 6, whose expression is repressed in two different murine models of PKD: the cpk and jck mouse [7]
Ke 6 Gene Expression Is Down-regulated in pcy Mice—The pcy mutation gives rise to a slowly progressing form of PKD [18], similar to the jck model [19] and unlike the cpk model [20], where the manifestation of the disease occurs soon after birth

Summary

Introduction

Polycystic kidney disease (PKD) is a major inherited cause of renal failure in humans. It is clear that polycystic kidney disease is a multigenetic disease, since numerous inherited diseases occur in both humans and mice which give rise to renal cysts caused by different genes. 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. The increased concentration of biologically active steroids is most likely responsible for initiating events that result in polycystic kidney disease [8]. Characterization of the Ke 6 gene promoter sequence offers the possibility of investigating the interaction of transcription factors and cis-regulatory elements responsible for its high level of expression in kidney and liver and its aberrant regulation in PKD.

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Results

Conclusion