Skip Navigation


Human Molecular Genetics Advance Access originally published online on August 19, 2009
Human Molecular Genetics 2009 18(22):4428-4441; doi:10.1093/hmg/ddp398
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
18/22/4428    most recent
ddp398v1
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 arrowRequest Permissions
Google Scholar
Right arrow Articles by Zhou, J.
Right arrow Articles by Parada, L. F.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhou, J.
Right arrow Articles by Parada, L. F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Loss of Tsc1, but not Pten, in renal tubular cells causes polycystic kidney disease by activating mTORC1

Jing Zhou1, James Brugarolas1,2 and Luis F. Parada1,*

1 Department of Developmental Biology and 2 Department of Internal Medicine, Division of Hematology-Oncology, and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA

* To whom correspondence should be addressed at: Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA. Tel: +1 2146481822; Fax: +1 2146481960; Email: luis.parada{at}utsouthwestern.edu

Received June 1, 2009; Accepted August 17, 2009

Tuberous sclerosis complex (TSC) is a genetic disorder linked to mutations of either the TSC1 or TSC2 gene, which encode proteins that form a complex to negatively regulate mammalian target of rapamycin complex 1 (mTORC1). Clinically, a small percentage of TSC patients develop severe infantile polycystic kidney disease (PKD), which is believed to be caused by deletion of the contiguous TSC2 and PKD1 genes on human chromosome 16. Recent studies have implicated the TSC/mTORC1 signaling pathway in PKD, but how dysfunction of the TSC/mTORC1 pathway induces PKD is not clear. We report a PKD mouse model created by knocking out Tsc1 in a subset of renal tubular cells. Extensive renal cyst formation in these mice is accompanied by broadly elevated mTORC1 activity in both cell autonomous and non-cell autonomous compartments. Furthermore, cyst development requires mTORC1 activation, as low dosage of rapamycin administration effectively blocks cyst formation. Interestingly, disruption of Pten, an upstream regulator of TSC1/TSC2, in the same cells, does not lead to PKD seemingly due to limited activation of mTORC1, suggesting that PTEN may not be a major upstream regulator of TSC/mTORC1 during early postnatal kidney development.


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




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.