Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2006-5-3
pubmed:abstractText
Eae5 in rats was originally identified in two F(2) intercrosses, (DA x BN) and (E3 x DA), displaying linkage to CNS inflammation and disease severity in experimental autoimmune encephalomyelitis (EAE), respectively. This region overlaps with an arthritis locus, Pia4, which was also identified in the (E3 x DA) cross. Two congenic strains, BN.DA-Eae5 and BN.DA-Eae5.R1, encompassing the previously described Eae5 and Pia4, were established. DA alleles within the chromosome 12 fragment conferred an increase in disease susceptibility as well as increased inflammation and demyelination in the CNS as compared with BN alleles. To enable a more precise fine mapping of EAE regulatory genes, we used a rat advanced intercross line between the EAE-susceptible DA strain and the EAE-resistant PVG.1AV1 strain. Linkage analysis performed in the advanced intercross line considerably narrowed down the myelin oligodendrocyte glycoprotein-EAE regulatory locus (Eae5) to a approximately 1.3-megabase region with a defined number of candidate genes. In this study we demonstrate a regulatory effect of Eae5 on MOG-EAE by using both congenic strains as well as fine mapping these effects to a region containing Ncf-1, a gene associated with arthritis. In addition to structural polymorphisms in Ncf-1, both sequence polymorphisms and expression differences were identified in CLDN4. CLDN4 is a tight junction protein involved in blood-brain barrier integrity. In conclusion, our data strongly suggests Ncf-1 to be a gene shared between two organ-specific inflammatory diseases with a possible contribution by CLDN4 in encephalomyelitis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
176
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6055-64
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16670314-Animals, pubmed-meshheading:16670314-Animals, Congenic, pubmed-meshheading:16670314-Antibody Specificity, pubmed-meshheading:16670314-Autoantibodies, pubmed-meshheading:16670314-Brain, pubmed-meshheading:16670314-Chromosome Mapping, pubmed-meshheading:16670314-Crosses, Genetic, pubmed-meshheading:16670314-Encephalomyelitis, Autoimmune, Experimental, pubmed-meshheading:16670314-Genetic Markers, pubmed-meshheading:16670314-Humans, pubmed-meshheading:16670314-Membrane Proteins, pubmed-meshheading:16670314-Myelin Proteins, pubmed-meshheading:16670314-Myelin-Associated Glycoprotein, pubmed-meshheading:16670314-NADPH Oxidase, pubmed-meshheading:16670314-Polymorphism, Single Nucleotide, pubmed-meshheading:16670314-Rats, pubmed-meshheading:16670314-Rats, Inbred BN, pubmed-meshheading:16670314-Spinal Cord
pubmed:year
2006
pubmed:articleTitle
Advanced intercross line mapping of Eae5 reveals Ncf-1 and CLDN4 as candidate genes for experimental autoimmune encephalomyelitis.
pubmed:affiliation
Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, SE-171 76 Stockholm, Sweden. Kristina.Becanovic@cmm.ki.se
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't