Resistance to experimental autoimmune myasthenia gravis in genetically inbred rats. Association with decreased amounts of in situ acetylcholine receptor-antibody complexes.
Genetically related susceptibility for experimental autoimmune myasthenia gravis was investigated in nine inbred strains of rats immunized with heterologous acetylcholine (AChR) from Torpedo californica. Wistar Munich and Fischer strain animals consistently developed severe, fatal disease associated with impaired neuromuscular transmission and increased sensitivity to low doses of curare. A lower incidence of disease was induced in Wistar Kyoto, ACI, Brown Norway, Buffalo, and Lewis strain animals. In contrast, Wistar Furth and Copenhagen strain animals were resistant to experimental autoimmune myasthenia gravis, electrophysiologic responses were normal, and animals were insensitive to curare. All strains of animals manifested equivalent amounts of serum antibody to AChR and total muscle AChR was reduced to the same extent in both resistant and susceptible animals. In contrast, the amount of antibody-bound AChR was greater in susceptible Wistar Munich animals than the amount observed in resistant Wistar Furth animals. These data suggest that impaired neurotransmission is correlated with the extent of antibody binding to the AChR. The discordance in the amount of antibody bound to the AChR of resistant and susceptible animals may result from heritable differences in antibody properties. Cross-breeding experiments with Wistar Munich and Wistar Furth animals show that resistance for development of experimental autoimmune myasthenia gravis is recessive and indicate that disease susceptibility is linked to one or two genetic loci.
Biesecker
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G
Department of Pathology and Laboratory Medicine, Hahnemann University, Philadelphia, PA 19102.
Koffler
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D
D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000235:genetics / Q000502:physiology*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004576:Electromyography; D005260:Female; D007113:Immunity, Innate; D009132:Muscles / Q000378:metabolism; D009157:Myasthenia Gravis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D051381:Rats; D011912:Rats, Inbred ACI; D011914:Rats, Inbred BN; D011915:Rats, Inbred BUF; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains / Q000235:genetics / Q000276:immunology*; D011920:Rats, Inbred WF; D011921:Rats, Inbred WKY; D011950:Receptors, Cholinergic / Q000235:genetics / Q000502:physiology*; D013045:Species Specificity; D014101:Torpedo
D001323:Autoantibodies; D011950:Receptors, Cholinergic