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J. Biol. Chem., Vol. 280, Issue 5, 3938-3945, February 4, 2005

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Cystic Renal Neoplasia Following Conditional Inactivation of Apc in Mouse Renal Tubular Epithelium^*

Chao-Nan Qian, Jared Knol, Peter Igarashi, Fangming Lin¶, Uko Zylstra||, Bin Tean Teh, and Bart O. Williams**

From the Laboratories of Cancer Genetics and ^**Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, Michigan 49508, the Departments of Internal Medicine and Division of Basic Sciences and ^¶Pediatrics, University of Texas, Southwestern Medical Center, Dallas, Texas 75390, and the ^||Department of Biology, Calvin College, Grand Rapids, Michigan 49546

Alterations in Wnt/-catenin signaling have been linked to abnormal kidney development and tumorigenesis. To gain more insights into the effects of these alterations, we created mice carrying a conditional deletion of the Apc tumor suppressor gene specifically in the renal epithelium. As expected, the loss of Apc leads to increased levels of -catenin protein in renal epithelium. Most of these mice die shortly after birth, and multiple kidney cysts were found upon histological examination. Only rarely did these animals survive to adulthood. Analysis of these adults revealed severely cystic kidneys associated with the presence of renal adenomas. Our results confirm an important role for proper regulation of Wnt/-catenin signaling in renal development and provide evidence that dysregulation of the pathway can initiate tumorigenesis in the kidney.

Received for publication, September 16, 2004 , and in revised form, November 18, 2004.

^* This work was supported in part by National Institutes of Health Grants DK-42921, DK-57328, and DK-67565. Further support was provided by the Van Andel Research Institute. 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 should be addressed: Van Andel Research Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503. Tel.: 616-234-5308; Fax: 616-234-5309; E-mail: bart.williams{at}vai.org.

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