Sequence polymorphisms in the chemokines Scya1 (TCA3), Scya2 (monocyte chemoattractant protein (MCP)-1), and Scya12 (MCP-5) are candidates for eae7, a locus controlling susceptibility to monophasic remitting/nonrelapsing experimental allergic encephalomyelitis

Experimental allergic encephalomyelitis (EAE), the principal animal model o f multiple sclerosis, is genetically controlled, To date, 13 diseasc-modify ing loci have been identified in the mouse by whole genome scanning using a n F-2 intercross between EAE-susceptible SJL/J and EAE-resistant B10(-)S/Dv Te mice. Two quantitative trait loci (QTL), eae6 and eae7, on chromosome II were identified by classical marker-specific linkage analysis and interval mapping. Both QTL were reported to be associated with severity and duratio n of clinical signs. ene7 was subsequently shown to be a unique locus contr olling the development of monophasic remitting/nonrelapsing EAE, In this st udy, composite interval mapping resolved eae6 into two linked QTL: eae6a at 0-13 ch I is associated with disease severity, and eae6b at 19-28 cM assoc iated with the duration of clinical signs, Additionally, composite interval mapping significantly refined the locations of eae6a, eae6b, and eae7, the reby facilitating systematic candidate gene screening by cDNA sequencing of SJL/J and B10.S/DVTe alleles. Sequence polymorphisms were not seen in Lif and IL12 beta, candidate genes for eae6a and eae6b, respectively. Similarly , cDNA sequence polymorphisms in Nos2, Scya3, Scya4, Scya5, Scya6, Scya7, S cya9, Scya10, and Scya11 were excluded as candidates for ene7, However, mul tiple sequence polymorphisms resulting in significant amino acid substituti ons were identified in Scya1 (TCA-3), Scya2 (monocyte chemoattractant prote in (MCP)-1), and Scya12 (MCP-5), Given the role of chemokines in EAE, these sequence polymorphisms are promising candidates for eae7, a locus associat ed with severity of clinical signs and susceptibility to the shorter, less severe monophasic remitting/nonrelapsing form of disease.