Skip Navigation


Human Molecular Genetics Advance Access originally published online on October 11, 2007
Human Molecular Genetics 2007 16(24):3188-3196; doi:10.1093/hmg/ddm299
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
16/24/3188    most recent
ddm299v1
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 ISI Web of Science
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 (14)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Lantinga-van Leeuwen, I. S.
Right arrow Articles by Peters, D. J.M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lantinga-van Leeuwen, I. S.
Right arrow Articles by Peters, D. J.M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice

Irma S. Lantinga-van Leeuwen1, Wouter N. Leonhard1, Annemieke van der Wal2, Martijn H. Breuning1, Emile de Heer2 and Dorien J.M. Peters1,*

1 Department of Human Genetics and 2 Department of Pathology, Leiden University Medical Center, Leiden 2300RC, The Netherlands

* To whom correspondence should be addressed. Tel: +31 715269490; Fax: +31 715268285; Email: d.j.m.peters{at}lumc.nl

Received August 14, 2007; Accepted October 8, 2007

Autosomal dominant polycystic kidney disease, caused by mutations in the PKD1 gene, is characterized by progressive deterioration of kidney function due to the formation of thousands of cysts leading to kidney failure in mid-life or later. How cysts develop and grow is currently unknown, although extensive research revealed a plethora of cellular changes in cyst lining cells. We have constructed a tamoxifen-inducible, kidney epithelium-specific Pkd1-deletion mouse model. Upon administration of tamoxifen to these mice, a genomic fragment containing exons 2–11 of the Pkd1-gene is specifically deleted in the kidneys and cysts are formed. Interestingly, the timing of Pkd1-deletion has strong effects on the phenotype. At 1 month upon gene disruption, adult mice develop only a very mild cystic phenotype showing some small cysts and dilated tubules. Young mice, however, show massive cyst formation. In these mice, at the moment of gene disruption, cell proliferation takes place to elongate the nephron. Our data indicate that Pkd1 gene deficiency does not initiate sufficient autonomous cell proliferation leading to cyst formation and that additional stimuli are required. Furthermore, we show that one germ-line mutation of Pkd1 is already associated with increased proliferation.


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
 J. Am. Soc. Nephrol.Home page
A. P. Bastos, K. Piontek, A. M. Silva, D. Martini, L. F. Menezes, J. M. Fonseca, I. I. Fonseca, G. G. Germino, and L. F. Onuchic
Pkd1 Haploinsufficiency Increases Renal Damage and Induces Microcyst Formation following Ischemia/Reperfusion
J. Am. Soc. Nephrol., November 1, 2009; 20(11): 2389 - 2402.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
G. Mollet, J. Ratelade, O. Boyer, A. O. Muda, L. Morisset, T. A. Lavin, D. Kitzis, M. J. Dallman, L. Bugeon, N. Hubner, et al.
Podocin Inactivation in Mature Kidneys Causes Focal Segmental Glomerulosclerosis and Nephrotic Syndrome
J. Am. Soc. Nephrol., October 1, 2009; 20(10): 2181 - 2189.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. Prasad, J. P. McDaid, F. W. K. Tam, J. L. Haylor, and A. C. M. Ong
Pkd2 Dosage Influences Cellular Repair Responses following Ischemia-Reperfusion Injury
Am. J. Pathol., October 1, 2009; 175(4): 1493 - 1503.
[Abstract] [Full Text] [PDF]

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
 J. Cell Sci.Home page
A. J. Streets, B. E. Wagner, P. C. Harris, C. J. Ward, and A. C. M. Ong
Homophilic and heterophilic polycystin 1 interactions regulate E-cadherin recruitment and junction assembly in MDCK cells
J. Cell Sci., May 1, 2009; 122(9): 1410 - 1417.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
S. J. Leuenroth and C. M. Crews
Targeting Cyst Initiation in ADPKD
J. Am. Soc. Nephrol., January 1, 2009; 20(1): 1 - 3.
[Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. Takakura, L. Contrino, A. W. Beck, and J. Zhou
Pkd1 Inactivation Induced in Adulthood Produces Focal Cystic Disease
J. Am. Soc. Nephrol., December 1, 2008; 19(12): 2351 - 2363.
[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]

Home page
 CJASNHome page
J. P. Calvet
Strategies to Inhibit Cyst Formation in ADPKD
Clin. J. Am. Soc. Nephrol., July 1, 2008; 3(4): 1205 - 1211.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. Shibazaki, Z. Yu, S. Nishio, X. Tian, R. B. Thomson, M. Mitobe, A. Louvi, H. Velazquez, S. Ishibe, L. G. Cantley, et al.
Cyst formation and activation of the extracellular regulated kinase pathway after kidney specific inactivation of Pkd1
Hum. Mol. Genet., June 1, 2008; 17(11): 1505 - 1516.
[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.