A model of Rheumatoid arthritis caused by deregulated expression of the human TNF-globin gene construct. Symptoms of the disease start to develop at 3-4 weeks of age and develop fully the disease by 10 weeks of age. Pathology in these mice is characterized by infiltration of inflammatory cells, synovial hyperplasia, cartilage destruction and bone erosions. (view the article).
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WT |
Tg197 |
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Phenotype of WT and Tg197 mice at 8 weeks of age. Distortion and swelling of the joints is evident in the Tg197
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The model develops 100% penetrance of the disease and provides a fast in vivo model of assessing the effectiveness of not only anti TNF therapies, but other biological and small chemical entities as well. This models is recommended by the FDA for screening potential Rheumatoid Arthritis candidate drugs (FDA-Guidance for Industry Document).
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WT |
Tg197 |
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Histologic examination of ankle joints. Infiltration of inflammatory cells, Synovial hyperplasia, Articular cartilage destruction and Bone erosions are the characteristics of the Tg197 histologic examination of ankle joints
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Administration of Infliximab (Remicade) or Enbrel (Etanercept), two marketed therapeutics for RA, show therapeutic efficacy in this model. (treatment starts at 6 weeks of age)
Administration of Infliximab, Enbrel and Adalimumab show prophylactic efficacy as well.(treatment starts at 3 weeks of age)
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Irrelevant IgG |
Enbrel |
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Comparison of an irrelevant IgG and Enbrel on
microscopic examination of ankle joints. |
Among some non TNF therapeutics that have been used in this model successfully are diacerein and dexamethasone (view this article) and a phospholipase II inhibitor (view this article).
Importantly, this model has been instrumental in introducing novel therapies in the market. Read a document to see how Tg197 was used for testing Infliximab (view the document).
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Chronic Arthritis
Tg5453 (human TNF)