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Abstract:
Mice of the inbred strain MRL/MpJ-lpr/lpr are affected by a systemic autoimmune disease and a spontaneously occurring polyarthritis. To characterize the arthritis a histopathological study was performed on the joints of the four limbs and of the spinal column of 7, 16, 22 and 28-week-old animals of both sexes. Polyarthritis, the severity of which increased with age was detected in all mice. Proliferation of the synovial lining cells, already evident in 7-week-old animals, was the initial lesion. In the majority of cases infiltrates containing lymphocytes with a few plasmocytes, histiocytes, polymorphonuclear neutrophils and eosinophils were detected later on. The most pronounced changes were observed in the hind-paws, the fore-paws, the knee and hip joints, paired articulations being symmetrically involved. A pannus was seen at the most in 10% of the joints leading to limited and superficial destruction of the cartilage. Rheumatoid nodules were not seen. From 16 weeks of age deposits of unknown nature, often surrounded by phagocytosing macrophages and/or neutrophils, were observed in the articular and/or extra-articular connective tissue and in the vessels. There was a positive correlation between their presence and the intensity of the arthritis. The articular lesions in our study differ from those in rheumatoid arthritis because they lacked the specific and characteristic histological features of the human disease.
Insights
Mice with autoimmune disease developed progressive polyarthritis, characterized by synovial cell proliferation and inflammatory infiltrates. Articular lesions showed some cartilage destruction but lacked features of human rheumatoid arthritis.
Area of Science:
- Immunology
- Pathology
- Rheumatology
Background:
- MRL/MpJ-lpr/lpr mice exhibit systemic autoimmune disease and spontaneous polyarthritis.
- Understanding the histopathological progression of this murine arthritis is crucial for autoimmune disease research.
Purpose of the Study:
- To histopathologically characterize the spontaneous polyarthritis in MRL/MpJ-lpr/lpr mice.
- To compare the observed lesions with human rheumatoid arthritis.
Main Methods:
- Histopathological examination of joints from MRL/MpJ-lpr/lpr mice at various ages (7, 16, 22, 28 weeks).
- Assessment of lesion severity, cell infiltration, pannus formation, cartilage destruction, and extra-articular deposits.
Main Results:
- Progressive polyarthritis was observed in all mice, increasing in severity with age.
- Initial lesions involved synovial lining cell proliferation, followed by inflammatory infiltrates (lymphocytes, plasmocytes, histiocytes, neutrophils, eosinophils).
- Deposits of unknown nature correlated with arthritis intensity, and lesions differed from human rheumatoid arthritis histology.
Conclusions:
- MRL/MpJ-lpr/lpr mice develop a distinct form of polyarthritis with age-related progression.
- The observed articular lesions, while significant, do not fully replicate the characteristic histopathology of human rheumatoid arthritis.
- This model provides insights into autoimmune-mediated joint inflammation but requires careful interpretation regarding direct human rheumatoid arthritis parallels.