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

被引：314

作者：

Olofsson, P

Holmberg, J

Tordsson, J

Lu, SM

Åkerström, B

Holmdahl, R

机构：

[1] Lund Univ, Sect Med Inflammat Res, S-22184 Lund, Sweden

[2] Lund Univ, Dept Cell & Mol Biol, Sect Mol Pathogenesis, S-22184 Lund, Sweden

来源：

NATURE GENETICS | 2003年 / 33卷 / 01期

关键词：

D O I：

10.1038/ng1058

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：25 / 32

页数：8

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