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Updated: May 23, 2026
Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
PR3 antibodies do not induce renal pathology in a novel PR3-humanized mouse model for Wegener's granulomatosis
Manfred Relle1, Hannes Cash, Nadine Schommers
1First Department of Medicine, University Hospital Johannes-Gutenberg University Mainz, Mainz, Germany. relle@uni-mainz.de
Abstract:
Different murine models have been used as basis for Proteinase 3 (PR3)-associated vasculitis models, but sufficient reproduction of the human clinical manifestation has failed to this date. As a reliable animal model is needed to further elucidate the pathological value of PR3-ANCA, we developed a PR3-humanized transgenic mouse model, in order to induce a glomerulonephritis. Our huPR3-transgenic mice were injected i.v. with our monoclonal antibodies, either unlabeled or directly labeled by fluorescein isothiocyanate. For a period of 5 days, proteinuria and erythrocyte count were measured with urine dip sticks. None of the mice exhibited proteinuria and/or an abnormal number of erythrocytes in the urine. Five days after antibody treatment, the mice were killed and different organs were fixed and immunohistochemically assessed. In the case of the kidney, we could detect a glomerulonephritis. Our study is able to show that although a direct renal target was given in transgenic human PR3 mice, no renal pathology was detectable. Multifactorial mechanisms for PR3-ANCA involvement in the development of Wegener's granulomatosis must be hypothesized.
Insights
Researchers developed a human Proteinase 3 (PR3) transgenic mouse model to study PR3-associated vasculitis. Despite inducing glomerulonephritis, the model did not show detectable renal pathology, suggesting complex mechanisms in Wegener's granulomatosis.
Area of Science:
- Immunology
- Nephrology
- Transgenic animal models
Background:
- Proteinase 3 (PR3)-associated vasculitis models in mice have historically failed to replicate human disease manifestations.
- A reliable animal model is crucial for understanding the pathological role of PR3-ANCA in vasculitis.
Purpose of the Study:
- To develop a PR3-humanized transgenic mouse model to investigate the induction of glomerulonephritis.
- To assess the direct renal pathology induced by anti-PR3 antibodies in this novel model.
Main Methods:
- Generation of PR3-humanized transgenic mice.
- Intravenous injection of unlabeled or fluorescein isothiocyanate-labeled monoclonal antibodies against PR3.
- Monitoring of proteinuria and erythrocyte counts for 5 days.
- Post-mortem immunohistochemical assessment of organs, particularly the kidneys.
Main Results:
- No proteinuria or abnormal erythrocyte counts were detected in the urine of treated mice.
- Glomerulonephritis was identified in the kidneys of the PR3-humanized mice.
- Despite the presence of a direct renal target, no overt renal pathology was observed.
Conclusions:
- The PR3-humanized transgenic mouse model, while capable of developing glomerulonephritis, did not exhibit detectable renal pathology under the tested conditions.
- The findings suggest that multifactorial mechanisms, beyond direct renal targeting, are likely involved in the pathogenesis of PR3-ANCA-associated Wegener's granulomatosis.
