Volume 22, Issue 2 pp. 156-165
Main Article

Necrotizing myopathy induced by overexpression of interferon-γ in transgenic mice

G. Diane Shelton DVM, PhD

Corresponding Author

G. Diane Shelton DVM, PhD

Department of Pathology, University of California, San Diego, La Jolla, California 92093-0612, USA

Department of Pathology, University of California, San Diego, La Jolla, California 92093-0612, USASearch for more papers by this author
Nigel A. Calcutt PhD

Nigel A. Calcutt PhD

Department of Pathology, University of California, San Diego, La Jolla, California 92093-0612, USA

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Robert S. Garrett MS

Robert S. Garrett MS

Veterans Administration Research Service, La Jolla, California, USA

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Danling Gu PhD

Danling Gu PhD

Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California, USA

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Nora Sarvetnick PhD

Nora Sarvetnick PhD

Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California, USA

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W. Marie Campana PhD

W. Marie Campana PhD

Department of Neurosciences, University of California, San Diego, La Jolla, California, USA

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Henry C. Powell MD, DSc

Henry C. Powell MD, DSc

Veterans Administration Research Service, La Jolla, California, USA

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Abstract

A transgenic mouse model has been established in which the cytokine interferon-γ (IFN-γ) is overexpressed through the action of the acetylcholine receptor epsilon promoter acting at the neuromuscular junction. While originally developed as a model for the study of the pathogenesis of myasthenia gravis, there are important differences from both human myasthenia gravis and its animal model, experimental autoimmune myasthenia gravis. By 4 months of age there was a well-established inflammatory, predominantly necrotizing myopathy, with marked dystrophic calcification. Dystrophic and degenerative changes in terminal axons and adjacent Schwann cells were also apparent. The acetylcholine receptor was not the primary target of the inflammatory response, since at 10 weeks of age the receptor content was not decreased and antibodies were not detected bound to the receptor. The IFNγ transgenic mouse model may provide a clinically relevant model of necrotizing myopathy for investigation of the pathological changes associated with, and presumably precipitated by, overexpression of the proinflammatory cytokine interferon-γ on the neuromuscular junction, intramuscular nerves and myofibers. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 156–165, 1999

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