SEVERE FIBRONECTIN-DEPOSIT RENAL GLOMERULAR-DISEASE IN MICE LACKING UTEROGLOBIN

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 o f predominantly multimeric fibronectin (Fn), The molecular mechanism t hat normally prevents Fn deposition appears to involve high-affinity b inding 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 rai ses the possibility that an analogous pathogenic mechanism may underli e genetic Fn-deposit human glomerular disease.