Cystin, a novel cilia-associated protein, is disrupted in the cpk mouse model of polycystic kidney disease

Academic Article


  • 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.
  • Published In


  • cystine animal cell animal model article autosomal recessive disorder axoneme bacterial artificial chromosome cell differentiation cell polarity cellular distribution ciliary body controlled study DNA determination DNA library DNA sequence gene disruption gene expression hepatobiliary system homozygosity kidney epithelium kidney polycystic disease microvillus mouse nonhuman nucleotide sequence penetrance phenotype priority journal protein analysis protein expression reverse transcription polymerase chain reaction sequence analysis transgene Amino Acid Sequence Animals Base Sequence Chromosome Mapping Cilia Cloning, Molecular Disease Models, Animal DNA, Complementary Homozygote Humans Membrane Proteins Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Knockout Mice, Mutant Strains Molecular Sequence Data Mutation Polycystic Kidney, Autosomal Dominant RNA, Messenger
  • Digital Object Identifier (doi)

    Author List

  • Hou X; Mrug M; Yoder BK; Lefkowitz EJ; Kremmidiotis G; D'Eustachio P; Beier DR; Guay-Woodford LM
  • Start Page

  • 533
  • End Page

  • 540
  • Volume

  • 109
  • Issue

  • 4