The purpose of this study is to evaluate nerve and muscle physiology and histopathology in a murine lupus model. Muscle strength, compound muscle action potentials (distal latency and amplitude), proximal limb muscle, sciatic nerve and joint specimens were studied in MRL/lpr (lupus model) and MRL/++ (control) mice. MRL/lpr mice showed decreased muscle strength (P < 10(-6, Wilcoxon rank sum), lower compound muscle action potential mean amplitude and prolonged distal latency (P = 0.005 and 0.042. Mann-Whitney U-test), and muscle and nerve inflammation (P = 0.002 and P = 0.037, Fisher's exact test) compared with MRL/++ mice. The MRL/lpr strain evaluated in this study demonstrated muscle weakness, abnormal motor nerve conduction studies and inflammation of both muscle and nerve. These features make it an excellent model for studying the neuromuscular complications of lupus.
Two methods were compared with regard to their ability to detect acetylcholine receptor-dependent neuromuscular dysfunction in rats with experimental autoimmune myasthenia gravis. In both cases, detection of AChR impairment required amplification of symptoms by administration of the AChR antagonist curare and appeared to be directly related to increasing levels of circulating anti-AChR antibodies. First, in vivo evaluations of decremental compound motor action potentials following repetitive nerve stimulation were performed by electromyography. Impaired neuromuscular function (i.e., greater than 10% decrement) was noted only after rats had been immunized twice with AChR, requiring levels of circulating anti-AChR antibody greater than about 200 micrograms/mL in serum. In contrast, the direct in vitro evaluation of stimulated isometric twitch tension appeared to be more sensitive in that impaired AChR-dependent muscle contraction was clearly observed following a single AChR immunization, and, as shown previously, required anti-AChR antibody levels of about 50 micrograms/mL in serum. Further discussion is presented concerning the advantages and disadvantages associated with each method of monitoring disease.
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