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 activity in metanephric organ culture disrupts branching morphogenesis of the ureteric bud, suggesting that gelB plays a role in kidney development in vivo. We studied kidneys of gelB-deficient mice to search for developmental, histological, molecular, ultrastructural, and functional defects. Surprisingly, no differences between gelB-/- and control kidneys were detected, and renal function was normal in gelB mutants. In addition, gelB-/- embryonic kidneys developed normally in organ culture. Gelatinase B-deficient mice were bred with Col4a3-/- mice, a model for Alport syndrome, to determine whether gelB influences the progression of glomerulonephritis. This is an important question, as it has been hypothesized that proteases are involved in damaging Alport glomerular basement membrane. However, the presence or absence of gelB did not affect the rate of progression of renal disease. Thus, gelB does not have a discernible role in the normal kidney and gelB is not involved in the progression of glomerulonephritis in a mouse model of Alport syndrome.
Andrews
K L
KL
Renal Division and the Division of Pulmonary and Critical Care Medicine, the Department of Internal Medicine, the Washington University School of Medicine, St. Louis, MO 63110, USA.
Betsuyaku
T
T
Rogers
S
S
Shipley
J M
JM
Senior
R M
RM
Miner
J H
JH
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure; D003094:Collagen / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D007668:Kidney / Q000196:embryology* / Q000201:enzymology / Q000648:ultrastructure; D007674:Kidney Diseases / Q000201:enzymology / Q000473:pathology*; D007677:Kidney Function Tests; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009394:Nephritis, Hereditary / Q000201:enzymology / Q000473:pathology*; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D003094:Collagen; D020780:Matrix Metalloproteinase 9