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Updated: Sep 28, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Role of matrix metalloproteinases in kidney development and glomerulopathy: lessons from transgenic mice
Brigitte Lelongt1, Pierre Ronco
1Unité INSERM 489 and Université Paris 6, Hôpital Tenon, Paris, France.
Abstract:
Matrix metalloproteinase-9 (MMP9) is required for renal organogenesis in vitro and is increased in various nephropathies. We analysed the renal phenotype of MMP9-deficient mice and their susceptibility to a murine model of proliferative glomerulonephritis. MMP9 deficiency resulted in adult mice in a 12% nephronic reduction. Histological appearance and renal function of these mice was normal up to 12 months, at which time histological lesions appeared. In addition, glomerulonephritis was more severe in MMP9-deficient mice than in their control 3-month-old mates. In particular, the extent of crescent formation and fibrin deposition was greater, which led us to show that fibrin is a critical substrate for MMP9. These data provide the first demonstration in vivo that MMP9 is required for nephron mass formation and renal function in elderly mice, and further evidence of a novel protective effect of MMP9 on the development of fibrin-induced glomerular lesions.
Insights
Matrix metalloproteinase-9 (MMP9) deficiency reduces nephron mass and impairs renal function in aging mice. MMP9 also protects against severe glomerulonephritis by degrading fibrin deposits.
Area of Science:
- Nephrology
- Molecular Biology
- Immunology
Background:
- Matrix metalloproteinase-9 (MMP9) plays a role in renal organogenesis and is implicated in nephropathies.
- The in vivo function of MMP9 in adult kidney health and disease is not fully understood.
Purpose of the Study:
- To investigate the renal phenotype of MMP9-deficient mice.
- To assess the susceptibility of MMP9-deficient mice to a murine model of proliferative glomerulonephritis.
Main Methods:
- Analysis of renal phenotype in MMP9-deficient mice.
- Induction of a murine model of proliferative glomerulonephritis.
Main Results:
- MMP9 deficiency led to a 12% reduction in nephron mass in adult mice.
- MMP9-deficient mice exhibited normal renal function and histology up to 12 months, with lesions appearing thereafter.
- Glomerulonephritis was more severe in MMP9-deficient mice, characterized by increased crescent formation and fibrin deposition.
- Fibrin was identified as a critical substrate for MMP9.
Conclusions:
- MMP9 is essential for nephron mass formation and renal function in aging mice.
- MMP9 has a protective role against the development of fibrin-induced glomerular lesions in glomerulonephritis.
