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: PMID:12461526   (View Abstract at PubMed)
DOI: DOI:10.1038/ng1058   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NCF1HumanExperimental Arthritis severityISONcf1 (Rattus norvegicus)DNA:missense mutations:cds:p.M106V and p.M153T (rat)RGD 
Ncf1RatExperimental Arthritis severityIAGP DNA:missense mutations:cds:p.M106V and p.M153T (rat)RGD 
Ncf1MouseExperimental Arthritis severityISONcf1 (Rattus norvegicus)DNA:missense mutations:cds:p.M106V and p.M153T (rat)RGD 
DARatrheumatoid arthritis MODEL: inducedIAGP  RGD 
DARatrheumatoid arthritis treatmentIAGP  RGD 
DA.E3-(D12Got46-D12Rat26)/RhdRatrheumatoid arthritis  IAGP compared to DA and E3 strainsRGD 
E3/ZtmRhdRatrheumatoid arthritis MODEL: controlIAGP compared to DA strainRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ncf1Ratrespiratory burst  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

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