Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization

Development
David A CanoMatthias Hebrok

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.

References

Jun 1, 1995·Journal of the American Society of Nephrology : JASN·G M FickP A Gabow
Jul 6, 1995·The New England Journal of Medicine·D Woo
Jul 29, 1993·The New England Journal of Medicine·P A Gabow
Apr 1, 1993·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·J NautaE D Avner
Jul 1, 1996·The American Journal of Physiology·C M SorensonM R Hammerman
Jan 1, 1996·Cell Biology International·D N WheatleyG E Strugnell
Dec 15, 1996·The Journal of Clinical Investigation·L GengJ Zhou
Jan 7, 1998·The Journal of Experimental Medicine·M TrudelV D'Agati
Apr 8, 1998·Current Opinion in Genetics & Development·K Willert, R Nusse
Feb 13, 1999·The Journal of Biological Chemistry·E KimG Walz
Apr 13, 1999·Neuroscience·M HändelV Höllt
Apr 14, 1999·Kidney International·N S MurciaE D Avner
Sep 25, 1999·The Journal of Biological Chemistry·Y CaiS Somlo
Oct 21, 1999·Biochimica Et Biophysica Acta·J Roose, H Clevers
Nov 24, 1999·The Journal of Clinical Investigation·Y Huan, J van Adelsberg
Mar 11, 2000·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·S M AliD P Brooks
Apr 20, 2000·Journal of the American Society of Nephrology : JASN·Lukas FoggensteinerRichard Sandford
Jul 8, 2000·Proceedings of the National Academy of Sciences of the United States of America·S Bonner-WeirJ J O'Neil
Sep 27, 2000·Journal of the American Society of Nephrology : JASN·Justin L RickerCarolyn A Rankin
Sep 27, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·C R ScogginsS D Leach
Mar 14, 2001·Seminars in Nephrology·J P Calvet, J J Grantham
Mar 17, 2001·Molecular Biology of the Cell·P D TaulmanB K Yoder
Mar 29, 2001·Journal of the American Society of Nephrology : JASN·Patricia D Wilson
Apr 27, 2001·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·K NakanishiN S Murcia
Nov 1, 2001·The Journal of Membrane Biology·H A Praetorius, K R Spring
Feb 8, 2002·American Journal of Physiology. Renal Physiology·Bradley K YoderDaniel F Balkovetz
Mar 29, 2002·Kidney International·Tevfik EcderCharles L Edelstein
Jul 13, 2002·The Journal of Pathology·Susan Bonner-Weir, Arun Sharma
Aug 23, 2002·Journal of the American Society of Nephrology : JASN·Peter Igarashi, Stefan Somlo
Sep 20, 2002·Journal of the American Society of Nephrology : JASN·Bradley K YoderLisa M Guay-Woodford
Oct 10, 2002·Kidney International·Vincent H GattoneRobert M Klein

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Citations

Jul 12, 2005·Cell and Tissue Research·Jens NürnbergerAndreas Kribben
Jun 4, 2011·Cell and Tissue Research·Evangelia Tasouri, Kerry L Tucker
Jan 30, 2008·Medical & Biological Engineering & Computing·Robert E PoelmannBeerend P Hierck
Oct 25, 2012·In Vitro Cellular & Developmental Biology. Animal·Julie A RhodesFarzad Esni
Feb 12, 2010·Nature·Stuart B SmithMichael S German
Oct 24, 2007·Nature Reviews. Molecular Cell Biology·Manfred FliegaufHeymut Omran
May 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sara CervantesMatthias Hebrok
Jan 10, 2012·Human Molecular Genetics·Qihong ZhangVal C Sheffield
May 18, 2007·Annual Review of Cell and Developmental Biology·Jonathan T Eggenschwiler, Kathryn V Anderson
Oct 3, 2006·Annual Review of Physiology·Peter Satir, Søren Tvorup Christensen
Mar 31, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Lili GuoJohn A Williams
Jan 14, 2012·Obstetrics and Gynecology International·Shakila Abdul-Majeed, Surya M Nauli
Mar 12, 2009·Nephron. Physiology·Iben R VelandSøren T Christensen
Mar 3, 2009·The Journal of Clinical Investigation·Norann A Zaghloul, Nicholas Katsanis
Apr 10, 2010·BMC Developmental Biology·Daniel Kopinke, L Charles Murtaugh
Jan 29, 2013·Cilia·Yi-Chun HsiaoRussell J Ferland
Feb 11, 2010·Journal of Cell Science·E Scott Seeley, Maxence V Nachury
May 30, 2008·Frontiers in Bioscience : a Journal and Virtual Library·Robert J Kolb, Surya M Nauli
Nov 14, 2013·Cellular and Molecular Life Sciences : CMLS·David A CanoAnabel Rojas
Sep 20, 2006·Proceedings of the National Academy of Sciences of the United States of America·Benedetta PeruzziDonald P Bottaro
Apr 3, 2014·The Journal of Clinical Investigation·Yangfan P LiuNicholas Katsanis
Feb 8, 2006·Advances in Anatomic Pathology·Michele BiscegliaAdalberto Sessa
Dec 30, 2014·Cell Metabolism·Edwin C OhNicholas Katsanis
Nov 7, 2008·The Journal of Investigative Dermatology·Jonathan M LehmanBradley K Yoder
Mar 4, 2008·Pathology, Research and Practice·Michal Klysik
Jan 19, 2008·The American Journal of Pathology·Anna-Rachel GallagherStefan Somlo
Oct 2, 2015·Molecular Biology of the Cell·Jovenal T San AgustinGeorge B Witman
Jan 30, 2007·Gastroenterology·David A CanoMartin Zenker
Feb 10, 2007·Matrix Biology : Journal of the International Society for Matrix Biology·S R McGlashanC A Poole
Apr 29, 2005·Molecular Reproduction and Development·Stefan C TeilmannSøren T Christensen
Jan 24, 2007·Traffic·Søren T ChristensenPeter Satir
Apr 9, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Lotte B PedersenSøren T Christensen
Jul 17, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Sonja K NielsenSøren Tvorup Christensen
Mar 28, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Stephen J Moorman, Ardon Z Shorr
Mar 28, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Jonathan M LehmanBradley K Yoder
Dec 9, 2009·Clinical Genetics·C A MokM Zhen
Jun 6, 2014·Birth Defects Research. Part C, Embryo Today : Reviews·Liwei Huang, Joshua H Lipschutz
May 28, 2014·Birth Defects Research. Part C, Embryo Today : Reviews·Philip diIorioAgata Jurczyk

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