Skip Navigation


Human Molecular Genetics Advance Access originally published online on February 9, 2008
Human Molecular Genetics 2008 17(11):1578-1590; doi:10.1093/hmg/ddn045
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
17/11/1578    most recent
ddn045v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (9)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Patel, V.
Right arrow Articles by Igarashi, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Patel, V.
Right arrow Articles by Igarashi, P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Acute kidney injury and aberrant planar cell polarity induce cyst formation in mice lacking renal cilia

Vishal Patel1, Ling Li2, Patricia Cobo-Stark1, Xinli Shao1, Stefan Somlo4,5, Fangming Lin2,3 and Peter Igarashi1,2,3,*

1 Department of Internal Medicine 2 Department of Pediatrics 3 Division of Basic Science, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA 4 Department of Internal Medicine 5 Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA

* To whom correspondence should be addressed at: Division of Nephrology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., MC 8856, Dallas, TX 75390-8856, USA. Tel: +1 2146482754; Fax: +1 2146482754; Email: peter.igarashi{at}utsouthwestern.edu

Received December 10, 2007; Revised February 1, 2008; Accepted February 7, 2008

Polycystic kidney disease (PKD) is an inherited disorder that is characterized by the accumulation of cysts in the renal parenchyma and progressive decline in renal function. Recent studies suggest that PKD arises from abnormalities of the primary cilium. We have previously shown that kidney-specific inactivation of the ciliogenic gene Kif3a during embryonic development produces kidney cysts and renal failure. Here, we used tamoxifen-inducible, kidney-specific gene targeting to inactivate Kif3a in the postnatal mouse kidney. Kidney-specific inactivation of Kif3a in newborn mice resulted in the loss of primary cilia and produced kidney cysts primarily in the loops of Henle, whereas inactivation in adult mice did not lead to the rapid development of cysts despite a comparable loss of primary cilia. The age-dependence and locations of the cysts suggested that cyst formation required increased rates of cell proliferation. To test this possibility, we stimulated cell proliferation in the adult kidney by inducing acute kidney injury and tubular regeneration. Acute kidney injury induced cyst formation in adult Kif3a mutant mice. Analysis of pre-cystic tubules in Kif3a mutant mice showed that the loss of cilia did not stimulate cell proliferation but instead resulted in aberrant planar cell polarity as manifested by abnormalities in the orientation of cell division. We conclude that primary cilia are required for the maintenance of planar cell polarity in the mammalian kidney and that acute kidney injury exacerbates cystic disease.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
A. Takakura, L. Contrino, X. Zhou, J. V. Bonventre, Y. Sun, B. D. Humphreys, and J. Zhou
Renal injury is a third hit promoting rapid development of adult polycystic kidney disease
Hum. Mol. Genet., July 15, 2009; 18(14): 2523 - 2531.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
H. Happe, W. N. Leonhard, A. van der Wal, B. van de Water, I. S. Lantinga-van Leeuwen, M. H. Breuning, E. de Heer, and D. J.M. Peters
Toxic tubular injury in kidneys from Pkd1-deletion mice accelerates cystogenesis accompanied by dysregulated planar cell polarity and canonical Wnt signaling pathways
Hum. Mol. Genet., July 15, 2009; 18(14): 2532 - 2542.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
C. S. Bonnet, M. Aldred, C. von Ruhland, R. Harris, R. Sandford, and J. P. Cheadle
Defects in cell polarity underlie TSC and ADPKD-associated cystogenesis
Hum. Mol. Genet., June 15, 2009; 18(12): 2166 - 2176.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
J. A. Jonassen, J. San Agustin, J. A. Follit, and G. J. Pazour
Deletion of IFT20 in the mouse kidney causes misorientation of the mitotic spindle and cystic kidney disease
J. Cell Biol., November 3, 2008; 183(3): 377 - 384.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
D. P. Wallace, M. T. Quante, G. A. Reif, E. Nivens, F. Ahmed, S. J. Hempson, G. Blanco, and T. Yamaguchi
Periostin induces proliferation of human autosomal dominant polycystic kidney cells through {alpha}V-integrin receptor
Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1463 - F1471.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
S. J. Leuenroth, N. Bencivenga, P. Igarashi, S. Somlo, and C. M. Crews
Triptolide Reduces Cystogenesis in a Model of ADPKD
J. Am. Soc. Nephrol., September 1, 2008; 19(9): 1659 - 1662.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.