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

G. Diane Shelton, Nigel A. Calcutt, Robert S. Garrett, Danling Gu, Nora Sarvetnick, W. Marie Campana, Henry C. Powell

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 IFN(γ) 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.

Original languageEnglish (US)
Pages (from-to)156-165
Number of pages10
JournalMuscle and Nerve
Volume22
Issue number2
DOIs
StatePublished - Feb 15 1999

Fingerprint

Neuromuscular Junction
Myasthenia Gravis
Cholinergic Receptors
Muscular Diseases
Interferons
Transgenic Mice
Autoimmune Experimental Myasthenia Gravis
Cytokines
Schwann Cells
Presynaptic Terminals
Animal Models
Antibodies

Keywords

  • Cytokine
  • Inflammatory
  • Myopathy
  • Necrotizing
  • Toxic
  • Ultrastructure

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

Cite this

Necrotizing myopathy induced by overexpression of interferon-γ in transgenic mice. / Shelton, G. Diane; Calcutt, Nigel A.; Garrett, Robert S.; Gu, Danling; Sarvetnick, Nora; Campana, W. Marie; Powell, Henry C.

In: Muscle and Nerve, Vol. 22, No. 2, 15.02.1999, p. 156-165.

Research output: Contribution to journalArticle

Shelton, G. Diane ; Calcutt, Nigel A. ; Garrett, Robert S. ; Gu, Danling ; Sarvetnick, Nora ; Campana, W. Marie ; Powell, Henry C. / Necrotizing myopathy induced by overexpression of interferon-γ in transgenic mice. In: Muscle and Nerve. 1999 ; Vol. 22, No. 2. pp. 156-165.
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