Experimental autoimmune encephalomyelitis in hybrids between Lewis and Brown Norway rats

The susceptibility to experimental autoimmune encephalomyelitis (EAE) in Lewis (Lew) and Brown Norway (BN) rats was studied in breeding experiments, evaluating EAE from clinical signs of the disease. The Lew strain is highly susceptible, the BN strain is resistant to EAE. F1 hybrids between the strains show an intermediate susceptibility as described by earlier authors. Back-cross experiments verify that susceptibility is inherited in a complex way, at least according to a two-gene model previously suggested. Analysis of the F1 hybrids showed a bi-modal distribution of clinical scores, one group of rats which appear to have the same degree of susceptibility as the Lew strain, and another group with very low susceptibility. Study of F2 rats produced by F1 rats with high or low susceptibility showed that this property was probably not inherited, arguing against a residual heterozygosity in the parental strains. As an alternative hypothetical explanation, the possibility of allogeneic exclusion of genes regulating suppression of EAE is discussed.