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Science 30 May 1997:
Vol. 276. no. 5317, pp. 1408 - 1412
DOI: 10.1126/science.276.5317.1408
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Reports

Severe Fibronectin-Deposit Renal Glomerular Disease in Mice Lacking Uteroglobin

Zhongjian Zhang, Gopal C. Kundu, Chiun-Jye Yuan, Jerrold M. Ward, Eric J. Lee, Francesco DeMayo, Heiner Westphal, Anil B. Mukherjee *

Despite myriads of biological activities ascribed to uteroglobin (UG), a steroid-inducible secreted protein, its physiological functions are unknown. Mice in which the uteroglobin gene was disrupted had severe renal disease that was associated with massive glomerular deposition of predominantly multimeric fibronectin (Fn). The molecular mechanism that normally prevents Fn deposition appears to involve high-affinity binding of UG with Fn to form Fn-UG heteromers that counteract Fn self-aggregation, which is required for abnormal tissue deposition. Thus, UG is essential for maintaining normal renal function in mice, which raises the possibility that an analogous pathogenic mechanism may underlie genetic Fn-deposit human glomerular disease.

Z. Zhang, G. C. Kundu, C.-J. Yuan, A. B. Mukherjee, Section on Developmental Genetics, Heritable Disorders Branch, National Institute of Child Health and Human Development (NICHD), National Insitutes of Health (NIH), Bethesda, MD 20892-1830, USA.
J. M. Ward, Veterinary and Tumor Pathology Section, Office of Laboratory Animal Science, National Cancer Instititute, Frederick, MD 21702-1201, USA.
E. J. Lee and H. Westphal, Laboratory of Mammalian Genetics and Development, NICHD, NIH, Bethesda, MD 20892-1830, USA.
F. DeMayo, Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
*   To whom correspondence should be addressed: E-mail: mukherja{at}cc1.nichd.nih.gov

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