Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine the differing susceptibility of C57BL/6J and C3H/HeJ mice to experimental autoallergic myasthenia gravis (EAMG), we have compared the pathogenicity of sera from the two strains. Mice were immunized with acetylcholine receptor from T. californica and muscle weakness assessed as the time mice were capable of running on an exercise drum following the administration of a sub-lethal dose of D-tubocurarine. 16 of 20 C57BL/6J and only 4 of 19 C3H/HeJ mice developed muscle weakness. However, anti-AChR antibody titres were similar in both strains. The effect of transfer of pooled immune sera from each strain to naive recipients was therefore compared. Transfer of pooled C57BL/6J sera to naive C3H/HeJ and C57BL/6J mice produced significant muscle weakness (P less than 0.001 & P less than 0.001 respectively). Transfer of pooled C3H/HeJ sera did not produce statistically significant muscle weakness in either strain. It is concluded that differences in disease susceptibility result from differences in antibody specificities of the major antibody populations, rather than differences in total antibody amounts or other factors.
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PMID:Susceptibility to murine experimental autoallergic myasthenia gravis: the role of antibody specificity. 373 22

Mice immunized with acetylcholine receptor (AChR) purified from Torpedo californica form anti-AChR antibodies and often develop muscular weakness and flaccid paralysis closely resembling the human disease myasthenia gravis. This condition, termed experimental myasthenia gravis (EMG), is strain dependent in that the frequency of paralysis is much greater in some strains than in others. Differences in the frequency of EMG might result from differences in the immune system or the neuromuscular junction. In these studies, we have identified two loci, the major histocompatibility complex (H-2) region on chromosome 17 and the region that contains the structural genes for the constant region of immunoglobulin heavy chains (IgCH region) on chromosome 12, which significantly effect the probability with which a mouse immunized with T. californica AChR can be expected to become paralyzed. One genotype (H-2b, Ig-1b) correlated with high susceptibility to EMG in four strains with three dissimilar backgrounds. These studies demonstrate that susceptibility to EMG is a heritable trait determined by at least two distinct loci that are linked to regions of the mouse genome that regulate immune responsiveness.
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PMID:Linkage between the frequency of muscular weakness and loci that regulate immune responsiveness in murine experimental myasthenia gravis. 677 45

Mice immunized with purified AChR (T. californica) invariably form anti-AChR antibodies and often develop a condition of extreme muscular weakness and flaccid paralysis. Pharmacological, physiological, and ultrastructural studies indicate that the pathophysiology of EMG in the mouse closely resembles that of human MG. The single episode of muscular weakness typically found in mouse EMG differs from the acute phase of rat EMG in that macrophages and other phagocytes do not appear to play an active role in the destruction of the neuromuscular junction. The frequency of paralysis in mice immunized with AChR is highly strain dependent and is not attributable to polymorphisms with respect to susceptibility to cholinergic blockade. The incidence of paralysis does not correlate with the magnitude of the humoral response to either T. californica or mouse AChR. Because both paralyzed and nonparalyzed mice form antibodies which are able to increase the rate of both junctional and extrajunctional AChR degradation, the mere presence of antibodies reactive with cell surface antigenic determinants of AChR is not sufficient for the induction of paralysis. While it is still possible that antibody-induced degradation of AChR may be necessary for the induction of paralysis, these studies rule out the possibility that antigenic modulation of AChR is sufficient to account for the induction of paralysis in mouse EMG. In the present studies alleles of the two loci were identified which significantly effect the probability with which mice immunized with AChR can be expected to become paralyzed, the MHC and the IgCH region. Because one genotype, H-2b, Ig-1b segregated with high susceptibility to EMG in four strains derived from three dissimilar backgrounds, these studies strongly suggest that susceptibility to the development of paralysis is a heritable trait determined by regions of the mouse genome which regulate immune responsiveness.
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PMID:Factors affecting the susceptibility of different strains of mice to experimental myasthenia gravis. 695 76

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.
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PMID:Experimental myasthenia gravis. A murine system. 735 Feb 47