RGD Reference Report - Advanced intercross line mapping suggests that ncf1 (ean6) regulates severity in an animal model of guillain-barre syndrome. - Rat Genome Database

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Advanced intercross line mapping suggests that ncf1 (ean6) regulates severity in an animal model of guillain-barre syndrome.

Authors: Huberle, A  Beyeen, AD  Ockinger, J  Ayturan, M  Jagodic, M  De Graaf, KL  Fissolo, N  Marta, M  Olofsson, P  Hultqvist, M  Holmdahl, R  Olsson, T  Weissert, R 
Citation: Huberle A, etal., J Immunol. 2009 Apr 1;182(7):4432-8.
RGD ID: 2306769
Pubmed: (View Article at PubMed) PMID:19299744
DOI: Full-text: DOI:10.4049/jimmunol.0803847

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.



Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

QTLs
Ean2  (Experimental allergic neuritis QTL 2)
Ean3  (Experimental allergic neuritis QTL 3)
Ean4  (Experimental allergic neuritis QTL 4)
Ean5  (Experimental allergic neuritis QTL 5)
Ean6  (Experimental allergic neuritis QTL 6)

Strains
Kini:DA,PVG-G12  (NA)

Objects referenced in this article
QTL Cia27 Collagen induced arthritis QTL 27 Rattus norvegicus
QTL Cia3 Collagen induced arthritis QTL 3 Rattus norvegicus
QTL Eae18a Experimental allergic encephalomyelitis QTL 18a Rattus norvegicus
QTL Eae5 Experimental allergic encephalomyelitis QTL 5 Rattus norvegicus
QTL Oia3 Oil induced arthritis QTL 3 Rattus norvegicus
QTL Oia4 Oil induced arthritis QTL 4 Rattus norvegicus
QTL Pia4 Pristane induced arthritis QTL 4 Rattus norvegicus

Additional Information