title: Identification of genomic regions controlling experimental autoimmune uveoretinitis in rats.
abstract: The present study attempts to identify specific genetic loci contributing to experimental autoimmune uveoretinitis (EAU) susceptibility in F2 progeny of resistant Fischer (F344/N) and susceptible Lewis (LEW/N) inbred rats. F2 progeny of F344/N x LEW/N inbred rats were immunized with the R16 peptide of interphotoreceptor retinoid-binding protein (IRBP). A genome-wide scan was conducted using 125 simple sequence length polymorphism markers in selected F2 animals that developed severe eye disease or remained unaffected to identify phenotype:genotype co-segregation. The F2 population (n = 1287) demonstrated a wide range of histologically assessed EAU scores (assessed on a scale of 0-4). The disease incidence and severity were not consistent with a simple Mendelian inheritance model. Of the F2 hybrid rats, 60% developed EAU, implying the existence of a potent susceptibility locus with incomplete penetrance associated with the LEW genome or a more complex polygenic model of 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 chromosomal regions. In conclusion, we have identified two genomic candidate intervals from D4Arb8 to D4Mit17 on chromosome 4 and from the chromosome end to D12Arb8 on chromosome 12, that appear to influence EAU susceptibility in LEW/F344 rats. Further analysis of these genomic regions may lead to identification of the susceptibility genes and to characterization of their function.
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018895:Microsatellite Repeats; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000235:genetics* / Q000276:immunology; D012177:Retinol-Binding Proteins / Q000276:immunology; D014605:Uveitis / Q000235:genetics* / Q000276:immunology