title: Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization.
abstract: Polycystic kidney disease (PKD) includes a group of disorders that are characterized by the presence of cysts in the kidney and other organs, including the pancreas. Here we show that in orpk mice, a model system for PKD that harbors a mutation in the gene that encodes the polaris protein, pancreatic defects start to occur at the end of gestation, with an initial expansion of the developing pancreatic ducts. Ductal dilation continues rapidly after birth and results in the formation of large, interconnected cysts. Expansion of pancreatic ducts is accompanied by apoptosis of neighboring acinar cells, whereas endocrine cell differentiation and islet formation appears to be unaffected. Polaris has been shown to co-localize with primary cilia, and these structures have been implicated in the formation of renal cysts. In the orpk pancreas, cilia numbers are reduced and cilia length is decreased. Expression of polycystin-2, a protein involved in PKD, is mislocalized in orpk mice. Furthermore, the cellular localization of beta-catenin, a protein involved in cell adhesion and Wnt signaling, is altered. Thus, polaris and primary cilia function are required for the maturation and maintenance of proper tissue organization in the pancreas.
authors.affiliation: Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Cano
authors.forename: Noel S
authors.initials: NS
authors.lastname: Murcia
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Pazour
authors.forename: Matthias
authors.initials: M
authors.lastname: Hebrok
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D002923:Cilia / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007515:Islets of Langerhans / Q000166:cytology / Q000196:embryology; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000196:embryology*; D007690:Polycystic Kidney Diseases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D050396:TRPP Cation Channels; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*; D051153:Wnt Proteins; D051176:beta Catenin; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D050396:TRPP Cation Channels; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D001616:beta-Galactosidase; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C098623:IFT88 protein, human; C114503:INVS protein, human; C491947:Invs protein, mouse; C490898:Tg737Rpw protein, mouse