-実験動物開発室-

Lysosomes in macrophages carry various degrading enzymes that digest the cellular components of dead cells. DNase II is a deoxyribonuclease that digests DNA and has optimal activity under acidic condition. A large amount of undigested DNA is observed in macrophages in the fetal liver of DNase2a^-/- mouse embryos and in the bone marrow of inducible DNase2a-deficient mice. Undigested DNA in the lysosomes activates macrophages to produce interferon-β, which causes lethal anemia in DNase2a^-/- embryos. Indeed, on E17.5, the number of red blood cells in DNase2a^-/- embryos is less than 10% of that observed in wild-type embryos [1, 2].

Inducible DNase2a-deficient mice and double-mutant mice lacking DNase II and the type I interferon receptor both appear normal at birth, but develop chronic polyarthritis resembling human rheumatoid arthritis [2, 3]. Histology of the affected joints shows cartilage destruction accompanied by the formation of a pannus-like structure. Genes for inflammatory cytokines, including TNF-α, IL-1β, and IL-6, are activated in the joints, and the administration of antibodies against these cytokines prevents the disease [4]. These mice provide the opportunity to understand the role of DNase II in the pathogenesis of human arthritis.