2.11. Collagen Induced Arthritis (CIA) and Adjuvant Induced Arthritis (AIA) Mouse Models

To induce adjuvant induced arthritis (AIA) in mice, 2 mg of complete Freund's adjuvant (CFA: Chondrex) was injected intradermally to 8-week-old C57BL/6 mice. KRN2 (3 mg/kg) was given to AIA mice via daily peritoneal injection, and swelling in the ankle and footpad was measured for 2 weeks. To induce Collagen induced arthritis (CIA) in mice, 8-week-old DBA/1J mice were immunized with bovine type II collagen (CII, Chondrex) emulsified in CFA on day 0. On day 14, a booster injection of CII in incomplete Freund's adjuvant (IFA, Chondrex) was given in the left footpad. After one week, KRN2 (3 mg/kg) was injected daily into the CIA mice. Other CII-immunized mice received KRN5 orally (15 mg/kg and 60 mg/kg) on alternate days. During the development of arthritis, clinical severity was scored daily as previously described (Kim et al., 2002). Paws and ankles were harvested on day 40, and the degrees of inflammation, synovial proliferation, and bone destruction were evaluated using a standard scoring protocol as previously described (Kim et al., 2002, Kong et al., 2010).