{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T05:35:36Z","timestamp":1792733736848,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,4,2]],"date-time":"2008-04-02T00:00:00Z","timestamp":1207094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>A subset of myasthenia gravis patients that are seronegative for anti\u2010acetylcholine receptor (anti\u2010AChR) antibodies are instead seropositive for antibodies against the muscle\u2010specific kinase (anti\u2010MuSK\u2013positive). Here, we test whether transfer of IgG from anti\u2010MuSK\u2013positive patients to mice confers impairment of the neuromuscular junction and muscle weakness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>IgG from anti\u2010MuSK\u2013positive myasthenia gravis patients or control IgG (seronegative for AChR and MuSK) was injected intraperitoneally (45mg daily for 14 days) into 6\u2010week\u2010old female FVB\/NJ and C57BL\/6J mice. Changes at neuromuscular junctions in the tibialis anterior and diaphragm muscles were assessed by confocal fluorescent imaging of AChRs stained with fluorescent\u2010\u03b1\u2010bungarotoxin. Loss of function was assessed by electromyography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In experimental mice injected with anti\u2010MuSK\u2013positive patient IgG, postsynaptic AChR staining was reduced to as little as 22% of that seen in control mice. Experimental mice showed reduced apposition of the nerve terminal (labeled with antibodies against synaptophysin and neurofilament) and the postsynaptic AChR cluster (labeled with fluorescent\u2010\u03b1\u2010bungarotoxin). Mice injected with IgG from two of three anti\u2010MuSK\u2013positive patients lost weight and developed muscle weakness associated with a decremental electromyographic trace on repetitive nerve stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>IgG from anti\u2010MuSK\u2013positive patients can cause myasthenia gravis when injected into mice. This may be explained by a progressive reduction in the density of postsynaptic AChR combined with changes in the nerve terminal and its relation to the postsynaptic structure. 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