Uteroglobin deficient mice - a novel animal model for IgA nephropathy?

The molecular mechanism(s) of immunoglobulin A (IgA) nephropathy, the most common primary renal glomerular disease worldwide, is unknown. Its patholog ic cultures include hematuria, high levels of circulating IgA-fibronectin ( Fn) complexes, and glomerular deposition of IgA, complement C3, Fn and coll agen. We report here that two independent mouse models (gene knockout and a ntisense transgenic), both manifesting deficiency of an anti-inflammatory p rotein, uteroglobin (UG), develop almost all of the pahtologic features of human IgA nephropathy. We further demonstrate that Fn-UG heteromerization, reported to prevent abnormal glomerular deposition of Fn and collagen, also abrogates both the formation of IgA-Fn complexes and their binding to glom erular cells. Moreover, UG prevents glomerular accumulation of exogenous IgA in UG-null m ice. These results define an essential role for;ir UG in preventing mouse I gA nephropathy and warrant further studies to determine if a similar mechan ism(s) underlies the human disease.