RGD Reference Report - Positional identification of Ncf1 as a gene that regulates arthritis severity in rats. - Rat Genome Database

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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.
RGD ID: 628543
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.

Disease Annotations    

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Ncf1  (neutrophil cytosolic factor 1)

Genes (Mus musculus)
Ncf1  (neutrophil cytosolic factor 1)

Genes (Homo sapiens)
NCF1  (neutrophil cytosolic factor 1)

Objects referenced in this article
Gene Gtf2i general transcription factor II I Rattus norvegicus
Gene Gtf2ird1 GTF2I repeat domain containing 1 Rattus norvegicus

Additional Information