Abnormal humoral responses toward motor end plate constituents in muscle induce myasthenia gravis (MG). To study the etiology of this disease, and whether it could be induced by host defense molecules, we examined the consequences of interferon (IFN) gamma production within the neuromuscular junction of transgenic mice. The transgenic mice exhibited gradually increasing muscular weakness, flaccid paralysis, and functional disruption of the neuromuscular junction that was reversed after administration of an inhibitor of acetylcholinesterase, features which are strikingly similar to human MG. Furthermore, histological examination revealed infiltration of mononuclear cells and autoantibody deposition at motor end plates. Immunoprecipitation analysis indicated that a previously unidentified 87-kD target antigen was recognized by sera from transgenic mice and also by sera from the majority of human MG patients studied. These results suggest that expression of IFN-gamma at motor end plates provokes an autoimmune humoral response, similar to human MG, thus linking the expression of this factor with development of this disease.
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1 February 1995
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February 01 1995
Myasthenia gravis-like syndrome induced by expression of interferon gamma in the neuromuscular junction.
D Gu,
D Gu
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
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L Wogensen,
L Wogensen
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
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N A Calcutt,
N A Calcutt
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
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C Xia,
C Xia
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
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S Zhu,
S Zhu
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
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J P Merlie,
J P Merlie
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
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H S Fox,
H S Fox
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
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J Lindstrom,
J Lindstrom
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
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H C Powell,
H C Powell
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
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N Sarvetnick
N Sarvetnick
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
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D Gu
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
L Wogensen
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
N A Calcutt
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
C Xia
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
S Zhu
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
J P Merlie
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
H S Fox
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
J Lindstrom
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
H C Powell
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
N Sarvetnick
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1995) 181 (2): 547–557.
Citation
D Gu, L Wogensen, N A Calcutt, C Xia, S Zhu, J P Merlie, H S Fox, J Lindstrom, H C Powell, N Sarvetnick; Myasthenia gravis-like syndrome induced by expression of interferon gamma in the neuromuscular junction.. J Exp Med 1 February 1995; 181 (2): 547–557. doi: https://doi.org/10.1084/jem.181.2.547
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