A single mutation in one gene can trigger autoimmune arthritis in mice, according to research in this week's Nature (Vol. 426, No. 6965, 27 Nov 03; pp. 454-460). The study may help us to understand the causes and molecular mechanisms of some forms of human rheumatoid arthritis.
Shimon Sakaguchi and colleagues studied SKG mice, a strain of mice that spontaneously develop chronic arthritis. The animals have a mutation in the ZAP-70 gene that affects T-cell signalling. Reactive T cells that would normally be lost during development remain, triggering joint inflammation.
Rheumatoid arthritis afflicts about 1% of the world population. Four out of 160 human patients tested positive for similar mutations. This suggests that ZAP-70 mutations may trigger rheumatoid arthritis in 2.5% of cases. The cause of the disease at large remains unknown. The study highlights the complex nature of autoimmune diseases. Genetics and the environment are likely to contribute to disease progression, the authors speculate.
Kyoto University and RIKEN, Japan
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