Gelatinase B (MMP-9) is not essential in the normal kidney and does not influence progression of renal disease in a mouse model of Alport syndrome

Matrix metalloproteinases are matrix degrading: enzymes implicated in many biological processes, including development and inflammation. Gelatinase B (gelB; also known as MMP-9) is expressed in the kidney and is hypothesized to be involved in basement membrane remodeling and in preventing pathogenic accumulation of extracellular matrix in the kidney. Inhibition of gelB act ivity in metanephric organ culture disrupts branching morphogenesis of the ureteric bud, suggesting that gelB plays a role in kidney development in vi vo. We studied kidneys of gelB-deficient mice to search for developmental, histological, molecular, ultrastructural, and functional defects. Surprisin gly, no differences between gelB-/- and control kidneys were detected, and renal function was normal in gelB mutants. in addition, gelB-/- embryonic k idneys developed normally In organ culture, Gelatinase B-deficient mice wer e bred with Col4a3-/- mice, a model for Alport syndrome, to determine wheth er gelB influences the progression of glomerulonephritis. This is an import ant question, as it has been hypothesized that proteases are involved in da maging Alport glomerular basement membrane. However, the presence or absenc e of gelB did not affect the rate of progression of renal disease. Thus, ge lB does not have a discernible role in the normal kidney and gelB is not in volved in the progression of glomerulonephritis In a mouse model of Alport syndrome.