Identification of genomic regions controlling experimental autoimmune uveoretinitis in rats

The present study attempts to identify specific genetic locicontributing to experimental autoimmune uveoretinitis (EAU)susceptibility in F₂ progeny of resistant Fischer (F344/N) andsusceptible Lewis (LEW/N) inbred rats. F₂ progeny of F344/Nx LEW/N inbred rats were immunized with the R16 peptide of interphotoreceptorretinoid-binding protein (IRBP). A genome-wide scan was conductedusing 125 simple sequence length polymorphism markers in selectedF₂ animals that developed severe eye disease or remained unaffectedto identify phenotype:genotype co-segregation. The F₂ population(n = 1287) demonstrated a wide range of histologically assessedEAU scores (assessed on a scale of 0–4). The disease incidenceand severity were not consistent with a simple Mendelian inheritancemodel. Of the F₂ hybrid rats, 60% developed EAU, implying theexistence of a potent susceptibility locus with incomplete penetranceassociated with the LEW genome or a more complex polygenic modelof inheritance. Two genomic regions, on chromosomes 4 and 12,showed strong genetic linkage to the EAU phenotype (P < 0.0016),suggesting the presence of susceptibility loci in these chromosomalregions. In conclusion, we have identified two genomic candidateintervals from D4Arb8 to D4Mit17 on chromosome 4 and from thechromosome end to D12Arb8 on chromosome 12, that appear to influenceEAU susceptibility in LEW/F344 rats. Further analysis of thesegenomic regions may lead to identification of the susceptibilitygenes and to characterization of their function.