Experimental myasthenia gravis. A murine system.
Mice from eight inbred strains were immunized with acetylcholine receptor (AChR) purified from Torpedo californica. All mice developed high concentrations of serum antibodies (10(-6) M) against the immunogen and approximately 80% possessed antibodies reactive with mouse nicotinic AChR. 33% of the mice immunized (n = 236) developed muscular weakness and flaccid paralysis. Behavioral, electrophysiological, and pharmacological similarities were found between the experimentally induced muscular weakness and the disease myasthenia gravis. Susceptibility to experimental myasthenia was found to be strain dependent in that the frequency of paralysis was much greater in some strains than others. The occurrence of muscular weakness and flaccid paralysis did not correlate with the concentration of antibodies reactive with T. californica or mouse AChR. Anti-receptor antibodies which increased the rate of AChR degradation on the mouse muscle cell line, BC3H-1, were found in the serum of both myasthenic and nonmyasthenic mice. 40% of the mice tested possessed antibodies reactive with antigenic determinants present on mouse receptor but not T. californica receptor. The occurrence of antibodies unique to mouse receptor did not correlate with myasthenia. Thus, myasthenia in the mouse does not occur simply as a consequence of the presence of antibodies directed against cell surface antigenic determinants of AChR. If anti-AChR antibodies are both necessary and sufficient for the induction of myasthenia, then these studies suggest that populations of a particular structure and/or specificity are required. It is anticipated that the mouse model of myasthenia gravis will permit the regulation of the anti-receptor immune response to be studied in detail.
D000109:Acetylcholine; D000818:Animals; D000917:Antibody Formation; D001327:Autoimmune Diseases; D002460:Cell Line; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D009132:Muscles / Q000276:immunology; D009157:Myasthenia Gravis / Q000188:drug therapy / Q000276:immunology*; D009388:Neostigmine / Q000627:therapeutic use; D011950:Receptors, Cholinergic; D012910:Snake Venoms
D011950:Receptors, Cholinergic; D012910:Snake Venoms; D009388:Neostigmine; D000109:Acetylcholine