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

Muscle Nerve. 1999 Feb;22(2):156-65. doi: 10.1002/(sici)1097-4598(199902)22:2<156::aid-mus3>3.0.co;2-u.

Abstract

A transgenic mouse model has been established in which the cytokine interferon-gamma (IFN-gamma) 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 IFNgamma 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 pro-inflammatory cytokine interferon-gamma on the neuromuscular junction, intramuscular nerves and myofibers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibodies / metabolism
  • Calcinosis / pathology
  • Disease Models, Animal
  • Histocytochemistry
  • Immunohistochemistry
  • Inflammation / pathology
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / genetics*
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron
  • Motor Endplate / pathology
  • Motor Endplate / ultrastructure
  • Motor Neurons / pathology
  • Motor Neurons / ultrastructure
  • Muscle, Skeletal / pathology*
  • Muscle, Skeletal / ultrastructure
  • Necrosis
  • Neuromuscular Diseases / genetics*
  • Neuromuscular Diseases / pathology*
  • Receptors, Cholinergic / analysis
  • Receptors, Cholinergic / metabolism

Substances

  • Antibodies
  • Receptors, Cholinergic
  • Interferon-gamma