Normal function and lack of fibronectin accumulation in kidneys of Clara cell secretory protein/uteroglobin deficient mice

Clara cell secretory protein (CCSP), also known as uteroglobin (Ug), is a 1 6-kDa homodimeric protein of unknown function. Within rodent species, CCSP is expressed predominantly by nonciliated Clara cells that line conducting airways of the lung. To investigate in vivo functions for CCSP, we establis hed mice homozygous for a null allele of the CCSP gene (CCSP-/-), We previo usly showed no overt phenotypic consequences associated with CCSP deficienc y when CCSP-/- mice are maintained in the absence of environmental stress. However, CCSP-/- mice show an oxidant-sensitive phenotype that cannot be at tributed to alterations in the inflammatory response when challenged by inh aled oxidant gases. The current study was undertaken to determine whether C CSP deficiency results in pathological changes to the kidney. This study wa s prompted by the recent description of severe systemic disease and kidney fibrosis/dysfunction in an independent line of CCSP-deficient mice, termed Ug-/- (Zhang et al, Science 276:1408-1412, 1997), CCSP-/- mice show normal growth and reproductive performance when maintained in two independent gene tic backgrounds, inbred 129 and congenic C57BL/6. Strain 129 CCSP-/- mice h ave normal kidney function, as assessed by urinary glucose, lactate dehydro genase, and glomerular filtration rate; they show no kidney fibrosis or abn ormalities in fibronectin accumulation and no histological abnormalities in proximal convoluted tubules or glomeruli at either light or electron micro scopic levels. CCSP deficiency is associated with mild proteinurea involvin g a modest increase in mouse major urinary protein-1. We conclude that CCSP (Ug) deficiency, per se, is not the cause of severe renal pathology and sy stemic disease reported for Ug-/- mice. (C) 1999 by the National Kidney Fou ndation, Inc.