Mouse collagen induced arthritis (CIA) is an experimental model of polyarthritis which has been widely used for preclinical testing of numerous anti-arthritic agents which are either under preclinical or clinical investigation or are currently used as therapeutics in this disease.
While mice (DBA/1lacJ, 1J or B10Rlll) reliably develop polyarthritis when immunized against bovine type II collagen using a variety of methodologies, we generally recommend immunizing DBA/1 mice on study day 0 and 21 (150 µL of bovine Type II collagen in Freund’s complete adjuvant) without concurrent boosting with endotoxin or recombinant IL-11,2.
Generally, mice show signs of disease between days 26 to 35 and the disease that occurs is usually not symmetrical and any combination of paws/joints may be affected. Lesions in affected joints resemble those occurring in rat collagen arthritis1.
Since caliper measurement of small mouse ankles is challenging, subjective clinical scoring systems are often used in conjunction with histologic scoring methods. Using the method listed below, clinical scores are given from days 18 to 35 in prophylactic dosing and from the first day of enrollment until necropsy in therapeutic dosing.
0 = Normal.
1 = One hind or fore paw joint affected or minimal diffuse erythema and swelling.
2 = Two hind or fore paw joints affected or mild diffuse erythema and swelling.
3 = Three hind or fore paw joints affected or moderate diffuse erythema and swelling.
4 = Four hind or fore paw joints affected or marked diffuse erythema and swelling.
5 = Entire paw affected, severe diffuse erythema and severe swelling, unable to flex digits.
Fore paws, hind paws/ankles, and knees are given scores of 0 through 5 for inflammation, pannus formation, cartilage damage and bone resorption according to these methods.
The Mouse CIA model has been particularly useful in evaluating the effects of clinically used biologic agents such as Interleukin-1 receptor antagonist (IL-1ra) and the soluble TNF receptors 3-7.
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