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

Olofsson, Peter LU ; Holmberg, Jens LU ; Tordsson, Jesper LU ; Lu, Shemin LU ; Åkerström, Bo LU and Holmdahl, Rikard LU (2003) In Nature Genetics 33(1). p.25-32
Abstract
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,... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Genetics
volume
33
issue
1
pages
25 - 32
publisher
Nature Publishing Group
external identifiers
  • wos:000180136100013
  • pmid:12461526
  • scopus:0037224772
ISSN
1546-1718
DOI
10.1038/ng1058
language
English
LU publication?
yes
id
215b7d3a-1283-4c51-bdc2-d03382bb4691 (old id 111649)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12461526&dopt=Abstract
date added to LUP
2007-06-26 11:38:05
date last changed
2018-02-11 03:57:02
@article{215b7d3a-1283-4c51-bdc2-d03382bb4691,
  abstract     = {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.},
  author       = {Olofsson, Peter and Holmberg, Jens and Tordsson, Jesper and Lu, Shemin and Åkerström, Bo and Holmdahl, Rikard},
  issn         = {1546-1718},
  language     = {eng},
  number       = {1},
  pages        = {25--32},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Positional identification of Ncf1 as a gene that regulates arthritis severity in rats.},
  url          = {http://dx.doi.org/10.1038/ng1058},
  volume       = {33},
  year         = {2003},
}