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Cell proliferation within Bowman's capsule in mice
Insights
Researchers developed a mouse model for crescentic glomerulonephritis, a severe kidney disease. This model will aid in studying cell proliferation
Area of Science:
- Nephrology
- Immunopathology
- Experimental Medicine
Background:
- Crescentic glomerulonephritis signifies severe glomerular damage with poor prognosis in humans.
- The role of macrophages in crescent formation is known, but cellular proliferation's contribution is understudied.
Purpose of the Study:
- To establish a reproducible mouse model of crescentic glomerulonephritis.
- To facilitate cell kinetic studies in the context of glomerular crescent development.
Main Methods:
- Mice were immunized with rabbit anti-mouse glomerular basement membrane (GBM) antiserum following pre-immunization with rabbit immunoglobulin G (IgG).
- A fibrinolytic inhibitor, Cyklokapron, was tested in some groups.
- Disease induction involved four daily intravenous injections of antiserum.
- Immunofluorescence detected IgG deposits in glomeruli.
Main Results:
- Extensive glomerular damage and crescent formation were induced, dose-dependently, within 3 days.
- Significant increases in glomerular size and cell numbers in Bowman's capsule were observed (P < 0.01).
- Mitotic indices rose to 0.8% by day 13.
Conclusions:
- A mouse model effectively replicates crescentic glomerulonephritis with significant cellular proliferation.
- This model is suitable for investigating the dynamics of cell proliferation in glomerular crescent formation.
Abstract:
Crescentic glomerulonephritis in man, irrespective of aetiology, indicates severe glomerular damage and carries a poor prognosis. The importance of the presence of macrophages in the development of glomerular crescents is well established, but the contribution of cellular proliferation in both macrophages and epithelial cells has received little attention. The purpose of this investigation was to develop a model of crescentic glomerulonephritis in mice, which will be suitable for cell kinetic studies. Preliminary studies are described, involving immunization with rabbit anti-mouse glomerular basement membrane (GBM) antiserum after pre-immunization with rabbit immunoglobulin G, both with and without treatment with a fibrinolytic inhibitor, Cyklokapron. Extensive glomerular damage, with crescent formation, was induced with four daily intravenous injections of rabbit anti-mouse GBM antiserum, after pre-immunization with rabbit IgG. The effect was shown to be dose dependent and was seen within 3 days of the last injection. Linear deposits of rabbit IgG were detected in all glomeruli by immunofluorescence and both linear and granular deposits of mouse IgG were also found. There was a significant increase in glomerular size and in the numbers of cells in Bowman's capsule (P less than 0.01), and increases in mitotic indices to 0.8 per cent were seen by day 13.