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Advanced Intercross Line Mapping Suggests That Ncf1 (Ean6) Regulates Severity in an Animal Model of Guillain-Barre Syndrome

Huberle, Alexander; Beyeen, Amennai Daniel; Ockinger, Johan; Ayturan, Miriam; Jagodic, Maja; de Graaf, Katrien L.; Fissolo, Nicolas; Marta, Monica; Olofsson, Peter and Hultqvist, Malin LU , et al. (2009) In Journal of Immunology 182(7). p.4432-4438
Abstract
We here present the first genetic fine mapping of experimental autoimmune neuritis (EAN), the animal model of Guillain-Barre syndrome, in a rat advanced intercross line. We identified and refined a total of five quantitative trait loci on rat chromosomes 4, 10, and 12 (RNO4, RNO10, RNO12), showing linkage to splenic IFN-gamma secretion and disease severity. All quantitative trait loci were shared with other models of complex inflammatory diseases. The quantitative trait locus showing strongest linkage to clinical disease was Ean6 and spans 4.3 Mb on RNO12, harboring the neutrophil cytosolic factor 1 (Ncf1) among other genes. Polymorphisms in Ncf1, a member of the NADPH oxidase complex, have been associated with disease regulation in... (More)
We here present the first genetic fine mapping of experimental autoimmune neuritis (EAN), the animal model of Guillain-Barre syndrome, in a rat advanced intercross line. We identified and refined a total of five quantitative trait loci on rat chromosomes 4, 10, and 12 (RNO4, RNO10, RNO12), showing linkage to splenic IFN-gamma secretion and disease severity. All quantitative trait loci were shared with other models of complex inflammatory diseases. The quantitative trait locus showing strongest linkage to clinical disease was Ean6 and spans 4.3 Mb on RNO12, harboring the neutrophil cytosolic factor 1 (Ncf1) among other genes. Polymorphisms in Ncf1, a member of the NADPH oxidase complex, have been associated with disease regulation in experimental arthritis and encephalomyelitis. We therefore tested the Ncf1 pathway by treating rats with a NADPH oxidase complex activator and ameliorated EAN compared the oil-treated control group. By proving the therapeutic effect of stimulating the NADPH oxidase complex, our data strongly suggest the first identification of a gene regulating peripheral nervous system inflammation. Taken together with previous reports, our findings suggest a general role of Ncf1 and oxidative burst in pathogenesis of experimental autoimmune animal models. The Journal of Immunology, 2009, 182: 4432-4438. (Less)
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Journal of Immunology
volume
182
issue
7
pages
4432 - 4438
publisher
American Association of Immunologists
external identifiers
  • wos:000264574600059
  • scopus:64249087896
ISSN
1550-6606
DOI
10.4049/jimmunol.0803847
language
English
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yes
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5ea91a9e-606c-4d95-b5b6-0b8dd79b2ffe (old id 1401476)
date added to LUP
2009-06-15 11:02:51
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@article{5ea91a9e-606c-4d95-b5b6-0b8dd79b2ffe,
  abstract     = {We here present the first genetic fine mapping of experimental autoimmune neuritis (EAN), the animal model of Guillain-Barre syndrome, in a rat advanced intercross line. We identified and refined a total of five quantitative trait loci on rat chromosomes 4, 10, and 12 (RNO4, RNO10, RNO12), showing linkage to splenic IFN-gamma secretion and disease severity. All quantitative trait loci were shared with other models of complex inflammatory diseases. The quantitative trait locus showing strongest linkage to clinical disease was Ean6 and spans 4.3 Mb on RNO12, harboring the neutrophil cytosolic factor 1 (Ncf1) among other genes. Polymorphisms in Ncf1, a member of the NADPH oxidase complex, have been associated with disease regulation in experimental arthritis and encephalomyelitis. We therefore tested the Ncf1 pathway by treating rats with a NADPH oxidase complex activator and ameliorated EAN compared the oil-treated control group. By proving the therapeutic effect of stimulating the NADPH oxidase complex, our data strongly suggest the first identification of a gene regulating peripheral nervous system inflammation. Taken together with previous reports, our findings suggest a general role of Ncf1 and oxidative burst in pathogenesis of experimental autoimmune animal models. The Journal of Immunology, 2009, 182: 4432-4438.},
  author       = {Huberle, Alexander and Beyeen, Amennai Daniel and Ockinger, Johan and Ayturan, Miriam and Jagodic, Maja and de Graaf, Katrien L. and Fissolo, Nicolas and Marta, Monica and Olofsson, Peter and Hultqvist, Malin and Holmdahl, Rikard and Olsson, Tomas and Weissert, Robert},
  issn         = {1550-6606},
  language     = {eng},
  number       = {7},
  pages        = {4432--4438},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Advanced Intercross Line Mapping Suggests That Ncf1 (Ean6) Regulates Severity in an Animal Model of Guillain-Barre Syndrome},
  url          = {http://dx.doi.org/10.4049/jimmunol.0803847},
  volume       = {182},
  year         = {2009},
}