Cystin, a novel cilia-associated protein, is disrupted in the cpk mouse model of polycystic kidney disease.
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.
Hou
Xiaoying
X
Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, USA.
Mrug
Michal
M
Yoder
Bradley K
BK
Lefkowitz
Elliot J
EJ
Kremmidiotis
Gabriel
G
D'Eustachio
Peter
P
Beier
David R
DR
Guay-Woodford
Lisa M
LM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002923:Cilia / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D006720:Homozygote; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation; D016891:Polycystic Kidney, Autosomal Dominant / Q000209:etiology / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
C449819:Cys1 protein, mouse; D018076:DNA, Complementary; D008565:Membrane Proteins; D012333:RNA, Messenger