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Publication : Collagen-induced arthritis is reduced in 5-lipoxygenase-activating protein-deficient mice.

First Author  Griffiths RJ Year  1997
Journal  J Exp Med Volume  185
Issue  6 Pages  1123-9
PubMed ID  9091585 Mgi Jnum  J:100736
Mgi Id  MGI:3589457 Doi  10.1084/jem.185.6.1123
Citation  Griffiths RJ, et al. (1997) Collagen-induced arthritis is reduced in 5-lipoxygenase-activating protein-deficient mice. J Exp Med 185(6):1123-9
abstractText  Collagen-induced arthritis in the DBA/1 mouse is an experimental model of human rheumatoid arthritis. To examine the role of leukotrienes in the pathogenesis of this disease, we have developed embryonic stem (ES) cells from this mouse strain. Here, we report that DBA/1 mice made deficient in 5-lipoxygenase-activating protein (FLAP) by gene targeting in ES cells develop and grow normally. Zymosan-stimulated leukotriene production in the peritoneal cavity of these mice is undetectable, whereas they produce substantial amounts of prostaglandins. The inflammatory response to zymosan is reduced in FLAP-deficient mice. The severity of collagen-induced arthritis in the FLAP-deficient mice was substantially reduced when compared with wild-type or heterozygous animals. This was not due to an immunosuppressive effect, because anti-collagen antibody levels were similar in wild-type and FLAP-deficient mice. These data demonstrate that leukotrienes play an essential role in both the acute and chronic inflammatory response in mice.
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