Cystin, a Novel Cilia-associated Protein, is Disrupted in the Cpk Mouse Model of Polycystic Kidney Disease

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2002 Feb 21

PMID 11854326

Citations 94

Authors

Xiaoying Hou

Michal Mrug

Bradley K Yoder

Elliot J Lefkowitz

Gabriel Kremmidiotis

Peter DEustachio

David R Beier

Lisa M Guay-Woodford

Affiliations

Soon will be listed here.

Abstract

The congenital polycystic kidney (cpk) mutation is the most extensively characterized mouse model of polycystic kidney disease (PKD). The renal cystic disease is fully expressed in homozygotes and is strikingly similar to human autosomal recessive PKD (ARPKD), whereas genetic background modulates the penetrance of the corresponding defect in the developing biliary tree. We now describe the positional cloning, mutation analysis, and expression of a novel gene that is disrupted in cpk mice. The cpk gene is expressed primarily in the kidney and liver and encodes a hydrophilic, 145-amino acid protein, which we term cystin. When expressed exogenously in polarized renal epithelial cells, cystin is detected in cilia, and its expression overlaps with polaris, another PKD-related protein. We therefore propose that the single epithelial cilium is important in the functional differentiation of polarized epithelia and that ciliary dysfunction underlies the PKD phenotype in cpk mice.

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