Poster Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Establishment and characterization of an auto-inflammatory disease model in mice (#329)

Takatsugu Oike 1 , Takeshi Miyamoto 1 , Hiroya Kanagawa 1 , Yasuo Niki 1 , Morio Matsumoto 1 , Masaya Nakamura 1
  1. Keio University School of Medicine, Shinjuku-ku, TOKYO, Japan

【Introduction】To date, several animal arthritis models such as Collagen-Induced Arthritis (CIA) and Adjuvant-Induced Arthritis (AIA) have been established. However, as there are diverse clinical subtypes in auto-immune diseases, these arthritis models can’t recapitulate all the auto-immune diseases, especially, auto-inflammatory syndrome, which is characterized by poly-arthritis in large joints, rash, fever and elevated white blood cells. Recently, IL-1 is implicated in the pathogenesis of auto-inflammatory syndrome. In this study, we generate new model mice and identify a therapeutic target.

【METHODS/RESULTS】We successfully generated conditional transgenic mice of human IL-1 (IL-1 cTg), in which human IL-1α was driven under a Cre/loxP system, in a C57/BL6 background. Arthritis development in large joints was seen in all IL-1 cTg mice one week after polyIpolyC administration with a 100% success rate under a C57/BL6 background, which is a difficult strain to develop arthritis. Micro CT analysis demonstrated the joint destructions in large joints in IL-1 cTg mice. Elevated white blood cell counts, dermatitis, and splenomegaly, all of which were characteristic phenotypes of auto-inflammatory syndrome, were detected in these mice. We found that serum IL-6 levels were elevated in those mice by a cytokine assay. Thus, IL-1 cTg mice were crossed with IL-6 knockout (IL-6 KO) mice to yield IL-1 cTg/IL-6 KO. Interestingly, the phenotypes seen in the IL-1 cTg mice were recovered in IL-1 cTg/IL-6 KO.

【conclusion】We successfully generated a new auto-inflammatory syndrome model, and showed that IL-6 may represent a therapeutic target to this syndrome.