Collagen Antibody-Induced Arthritis Studies in Mice
In this 21-day study, which bypasses the development of anti-collagen antibodies, arthritis is induced using a cocktail of monoclonal antibodies directed against type II collagen. Modeled after human rheumatoid arthritis, a key advantage of this model is its ability to induce the disease in many strains of mice that are resistant to the traditional collagen-induced arthritis methods.
Another advantage of this model is that compound assessment can be completed in a relatively short period of time. In standard collagen-induced arthritis protocols, the disease doesn't appear until 3–4 weeks and a typical study might last 6–8 weeks. In collagen antibody-induced arthritis, the disease appears within 7–8 days and studies can be completed within 18 days. An additional 7 days can be added to assess the effects of agents on the resolution phase of the disease.
Collagen antibody-induced arthritis relies on the injection of a cocktail of monoclonal antibodies directed against type II collagen (C-II), followed by a single injection of LPS. In animals, a significant part of the inflammatory attack on the joints is mediated by pathogenic antibodies directed against C-II. Collagen antibody-induced arthritis is dependent on IL-1β and TNF-α, but is independent of the effects of IL-6.
Disease activity is assessed by measuring inflammation swelling in the affected joints (paw volume or thickness) over time. Treatments can be assessed in either prophylactic or therapeutic testing paradigms. Clinical scoring is accomplished by awarding a score of 1 for each swollen digit, a score of 5 for a swollen footpad and a score of 5 for a swollen wrist or ankle. These are added together to give a maximal score of 60 for each animal.