Transgenic mice for interleukin 3 develop motor neuron degeneration associated with autoimmune reaction against spinal cord motor neurons

Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11354-9. doi: 10.1073/pnas.95.19.11354.

Abstract

Interleukin 3 (IL-3) stimulates the proliferation and differentiation of various haematopoietic progenitor cells. Recently, IL-3 and other cytokines were reported to exert a neurotrophic activity and to be associated with neurological disorders, suggesting their complex role in the central nervous system. We now show that overexpression of IL-3 in transgenic mice causes a motor neuron disease with several features of amyotrophic lateral sclerosis and progressive muscular atrophy. These animals exhibit hind limb paralysis at 7 months of age, associated with dendritic and axonal degeneration, loss of motor neurons in the spinal cord, and autoimmune reaction against these cells. We examined the effect of IL-3 on embryonic motor neurons survival in mixed spinal cord cultures. Our results suggest that motor neuronal degeneration is not directly triggered by the high level of expression of IL-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Animals
  • Autoimmunity / immunology*
  • Brain / pathology
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Histocytochemistry
  • Immunohistochemistry
  • Interleukin-3 / pharmacology*
  • Mice
  • Mice, Transgenic
  • Motor Neuron Disease / genetics
  • Motor Neurons / drug effects
  • Motor Neurons / immunology
  • Motor Neurons / pathology*
  • Muscular Atrophy / genetics
  • Paralysis / genetics
  • Spinal Cord / pathology

Substances

  • Interleukin-3