Genetic resistance to the induction of experimental allergic encephalomyelitis in Lewis rats. I. Genetic analysis of an apparent mutant strain with phenotypic resistance to experimental allergic encephalomyelitis.

Abstract

Clinical resistance to the induction of experimental allergic encephalomyelitis was observed in a closed colony of Lewis (designated Le-R) rats. Disease susceptibility in randomly bred animals appeared to increase with increasing age. In the small group of young Le-R rats, which were susceptible, disease onset was delayed, severity of symptoms was reduced, and duration of clinical signs was abbreviated compared to conventional Lewis rats. The severity of histologic neural tissue lesions correlated with clinical observations. Breeding experiments indicated that most Le-R rats were resistant to disease induction regardless of whether their ancestors had been selected for susceptibility or resistance. The F3 generation of resistant lineage was uniformly resistant at all ages tested. Virtually all (Lewis X Le-R)F1 rats of either sex were resistant when challenged at 7-8 wk of age indicating that resistance was a dominant autosomal trait. Approximately half of (F1 X Lewis) backcross rats developed paralytic EAE whereas one-fourth were entirely resistant, suggesting that disease resistance may be mediated by one or two genes. Le-R rats shared at least some of the Lewis rat major histocompatibility antigens. Resistance apparently did not reflect a nonspecific impairment of cellular immune responsiveness. Le-R rats, which had been challenged with myelin basic protein, developed antigen-reactive cells specific for basic protein or its encephalitogenic fragment. Spleen cells obtained from basic protein-sensitized Le-R rats did not adoptively transfer disease into Lewis rats. In contrast, spleen cells obtained from basic protein-sensitized Lewis rats readily transferred disease into both Lewis and Le-R recipients. These data suggest that disease resistance may be a result of an immunologic deficit (or suppressor cell activity) expressed during the differentiation of antigen-reactive cells into disease-inducing effector cells.

Genetics of Experimental Autoimmune Encephalomyelitis

“…Although LEW rats are susceptible to disease induction, a closed colony of Lewis rats was found to have become resistant to EAE and the strain was named Le-R [90]. The resistance in these rats decreases with age.…”

Inheritance of susceptibility to experimental autoimmune encephalomyelitis

“…Levine and Sowinski (1 973) Linthicum and Frelinger (1982), Fritz et al (1985) Levine and Sowinski (1978), Fritz et al (1985), Fritz and McFarlin (1989) Levine and Sowinski (1973) Teitelbaum et al (1978) Baker et al (1995 Levine et al (1966), Gasser et al (1973Gasser et al ( ,1975 Williams and Moore (1973), Gunther et al (1978), Lindh and Kallen (1978), Moore et al (1980), Waxman et al (1981). Happ et al (1988), Levine and Saltzman (1989) al.…”

“…Although LEW rats are susceptible to disease induction, a closed colony of Lewis rats was found to have become resistant to EAE and the strain was named Le-R (Waxman et al, 1981). The resistance in these rats decreases with age.…”