HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 20, 19986-19991, May 20, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/20/19986    most recent M501689200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, Y. Articles by Chung, S. S. M. Search for Related Content PubMed PubMed Citation Articles by Wang, Y. Articles by Chung, S. S. M. Social Bookmarking                      What's this?

Transgenic Mice Expressing Dominant-negative Osmotic-response Element-binding Protein (OREBP) in Lens Exhibit Fiber Cell Elongation Defect Associated with Increased DNA Breaks^*

Yu Wang¶, Ben C. B. Ko||, James Y. Yang**, Terrence T. L. Lam**, Zhirong Jiang**, Jinsong Zhang¶, Sookja K. Chung**, and Stephen S. M. Chung**

From the Department of Chemistry, the Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, and the ^**Institute of Molecular Biology, The University of Hong Kong, Hong Kong Special Administrative Region and the ^¶Department of Ophthalmology, Fourth Affiliated Hospital, China Medical University, Shenyang, China

Osmotic-response element-binding protein (OREBP), also known as TonEBP or NFAT5, is thought to be responsible for the induction of osmolyte-accumulating genes when cells are under hypertonic stress. Recent studies suggest that OREBP also plays a role in water reabsorption in the kidney, T-cell proliferation, and embryonic development. We developed transgenic mice that express the dominant-negative OREBP (OREBPdn) specifically in the lens because our earlier studies showed that it is particularly sensitive to osmotic stress. The transgenic mice developed nuclear cataract soon after birth, suggesting defects in lens development. The developing transgenic lenses showed incomplete elongation of fiber cells and formation of vacuoles. This is accompanied by evidence of DNA strand breaks, activation of p53, and induction of checkpoint kinase, suggesting that the developing fiber cells lacking OREBP are in a similar physiological state as cells experiencing hypertonic stress. These results indicate that OREBP-mediated accumulation of osmolytes is essential during elongation of the lens fiber cells.

Received for publication, February 14, 2005 , and in revised form, March 17, 2005.

^* This work was supported by University Grants Committee of the Hong Kong Special Administrative Region Areas of Excellence Scheme Grant AoE/P-10/01, by the University of Hong Kong Generic Drugs Research Program, by Research Grant Council Grants HKU 7390/04 M (to S. S. M. C.), HKU 7419/03 M (to B. C. B. K.), and HKU 7832/00 M (to J. Y. Y.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence may be addressed. E-mail: cbko{at}hkucc.hku.hk. To whom correspondence may be addressed. E-mail: yyang{at}hkucc.hku.hk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Xu, C. C. L. Wong, E. H. Y. Tong, S. S. M. Chung, J. R. Yates III, Y. Yin, and B. C. B. Ko Phosphorylation by Casein Kinase 1 Regulates Tonicity-induced Osmotic Response Element-binding Protein/Tonicity Enhancer-binding Protein Nucleocytoplasmic Trafficking J. Biol. Chem., June 20, 2008; 283(25): 17624 - 17634. [Abstract] [Full Text] [PDF]

				M. B. Burg, J. D. Ferraris, and N. I. Dmitrieva Cellular Response to Hyperosmotic Stresses Physiol Rev, October 1, 2007; 87(4): 1441 - 1474. [Abstract] [Full Text] [PDF]

				K. Kosuge, A. I. Chuang, S. Uematsu, K. P. Tan, K. Ohashi, B. C.B. Ko, and S. Ito Discovery of Osmosensitive Transcriptional Regulation of Human Cytochrome P450 3As by the Tonicity-Responsive Enhancer Binding Protein (Nuclear Factor of Activated T Cells 5) Mol. Pharmacol., October 1, 2007; 72(4): 826 - 837. [Abstract] [Full Text] [PDF]

				T. Ito, K. Asakura, K. Tougou, T. Fukuda, R. Kubota, S. Nonen, Y. Fujio, and J. Azuma Regulation of Cytochrome P450 2E1 under Hypertonic Environment through TonEBP in Human Hepatocytes Mol. Pharmacol., July 1, 2007; 72(1): 173 - 181. [Abstract] [Full Text] [PDF]

				T. Ito, Y. Fujio, K. Takahashi, and J. Azuma Degradation of NFAT5, a Transcriptional Regulator of Osmotic Stress-related Genes, Is a Critical Event for Doxorubicin-induced Cytotoxicity in Cardiac Myocytes J. Biol. Chem., January 12, 2007; 282(2): 1152 - 1160. [Abstract] [Full Text] [PDF]

				R. S. O'Connor, S. T. Mills, K. A. Jones, S. N. Ho, and G. K. Pavlath A combinatorial role for NFAT5 in both myoblast migration and differentiation during skeletal muscle myogenesis J. Cell Sci., January 1, 2007; 120(1): 149 - 159. [Abstract] [Full Text] [PDF]

				T.-T. Tsai, K. G. Danielson, A. Guttapalli, E. Oguz, T. J. Albert, I. M. Shapiro, and M. V. Risbud TonEBP/OREBP Is a Regulator of Nucleus Pulposus Cell Function and Survival in the Intervertebral Disc J. Biol. Chem., September 1, 2006; 281(35): 25416 - 25424. [Abstract] [Full Text] [PDF]