Identification of genomic regions controlling experimental autoimmune uveoretinitis in rats

The present study attempts to identify specific genetic loci contributing t o experimental autoimmune uveoretinitis (EAU) susceptibility in F-2 progeny of resistant Fischer (F344/N) and susceptible Lewis (LEW/N) inbred rats. F -2 progeny of F344/N x LEW/N inbred rats were immunized with the R16 peptid e of interphotoreceptor retinoid-binding protein (IRBP), A genome-wide scan was conducted using 125 simple sequence length polymorphism markers in sel ected F-2 animals that developed severe eye disease or remained unaffected to identify phenotype:genotype cosegregation. The F-2 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 F-2 hybrid rats, 60% deve loped EAU, implying the existence of a potent susceptibility locus with inc omplete penetrance associated with the LEW genome or a more complex polygen ic model of inheritance. Two genomic regions, on chromosomes 4 and 12, show ed strong genetic linkage to the EAU phenotype (P < 0.0016), suggesting the presence of susceptibility loci in these chromosomal regions. In conclusio n, we have identified two genomic candidate intervals from D4Arb8 to D4Mit1 7 on chromosome 4 and from the chromosome end to D12Arb8 on chromosome 12, that appear to influence EAU susceptibility in LEW/F344 rats. Further analy sis of these genomic regions may lead to identification of the susceptibili ty genes and to characterization of their function.