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Positioning of a Po...
Positioning of a Polymorphic Quantitative Trait Nucleotide in the Ncf1 Gene Controlling Oxidative Burst Response and Arthritis Severity in Rats
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- Hultqvist, Malin (författare)
- Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Redoxis AB, Lund Life Science Incubator, Lund, Sweden
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- Sareila, Outi (författare)
- Karolinska Institutet
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- Vilhardt, Frederik (författare)
- Institute for cellular and molecular medicine, The Panum Institute, Copenhagen University, Copenhagen, Denmark
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- Norin, Ulrika (författare)
- Karolinska Institutet
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- Olsson, Lina (författare)
- Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Medical Inflammation Research, C12 BMC, Lund University, Lund, Sweden
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- Olofsson, Peter (författare)
- Redoxis AB, Sahlgrenska Science Park, Go¨ teborg, Sweden
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- Hellman, Ulf (författare)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Holmdahl, Rikard (författare)
- Karolinska Institutet,Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Medical Inflammation Research, C12 BMC, Lund University, Lund, Sweden
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(creator_code:org_t)
- Mary Ann Liebert Inc, 2011
- 2011
- Engelska.
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 14:12, s. 2373-2383
- Relaterad länk:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- The Ncf1 gene, encoding the P47(PHOX) protein that regulates production of reactive oxygen species (ROS) by the phagocyte NADPH oxidase (NOX2) complex, is associated with autoimmunity and arthritis severity in rats. We have now identified that the single-nucleotide polymorphism (SNP) resulting in an M153T amino acid substitution mediates arthritis resistance and thus explains the molecular polymorphism underlying the earlier identified Ncf1 gene effect. We identified the SNP in position 153 to regulate ROS production using COSPHOX cells transfected with mutated Ncf1. To determine the role of this SNP for control of arthritis, we used the Wistar strain, identified to carry only the postulated arthritis resistant SNP in position 153. When this Ncf1 allele was backcrossed to the arthritis susceptible DA strain, both granulocyte ROS production and arthritis resistance were restored. Position 153 is located in the hinge region between the PX and SH3 domains of P47(PHOX). Mutational analysis of this position revealed a need for an -OH group in the side chain but we found no evidence for phosphorylation. The polymorphism did not affect assembly of the P47(PHOX)/P67(PHOX) complex in the cytosol or membrane localization, but is likely to operate downstream of assembly, affecting activity of the membrane NOX2 complex.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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