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Positional identification of Ncf1 as a gene that regulates arthritis severity in rats.

Authors: Olofsson, P  Holmberg, J  Tordsson, J  Lu, S  Akerstrom, B  Holmdahl, R 
Citation: Olofsson P, etal., Nat Genet 2003 Jan;33(1):25-32.
Pubmed: (View Article at PubMed) PMID:12461526
DOI: Full-text: DOI:10.1038/ng1058

The identification of genes underlying quantitative-trait loci (QTL) for complex diseases, such as rheumatoid arthritis, is a challenging and difficult task for the human genome project. Through positional cloning of the Pia4 QTL in rats, we found that a naturally occurring polymorphism of Ncf1 (encoding neutrophil cytosolic factor 1, a component of the NADPH oxidase complex) regulates arthritis severity. The disease-related allele of Ncf1 has reduced oxidative burst response and promotes activation of arthritogenic T cells. Pharmacological treatment with substances that activate the NADPH oxidase complex is shown to ameliorate arthritis. Hence, Ncf1 is associated with a new autoimmune mechanism leading to severe destructive arthritis, notably similar to rheumatoid arthritis in humans.

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CRRD Object Information
CRRD ID: 628543
Created: 2003-02-05
Species: All species
Last Modified: 2003-02-05
Status: ACTIVE



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