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
