Transgenic mice for interleukin 3 develop motor neuron degeneration associated with autoimmune reaction against spinal cord motor neurons.
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.
Chavany
C
C
Genetics and Molecular Immunology Section, Laboratory of Immunology/National Eye Institute, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda MD 20892, USA.
Vicario-Abejón
C
C
Miller
G
G
Jendoubi
M
M
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D001921:Brain / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006651:Histocytochemistry; D007150:Immunohistochemistry; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D016472:Motor Neuron Disease / Q000235:genetics; D009046:Motor Neurons / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D009133:Muscular Atrophy / Q000235:genetics; D010243:Paralysis / Q000235:genetics; D013116:Spinal Cord / Q000473:pathology
D007377:Interleukin-3