Nature Genetics
13, 43 - 47 (1996)
doi:10.1038/ng0596-43
Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injuryAndrew. G. Reaume1, Jeffrey L. Elliott2, Eric K. Hoffman1, Neil W. Kowall3, Robert J. Ferrante3, Donald R Siwek3, Heide M. Wilcox1, Dorothy G. Flood1, M. Flint Beal4, Robert H. Brown Jr.5, Richard W. Scott1
& William D. Snider2
1Dept. of Molecular Biology, Cephalon Inc., 145Brandywine Pkwy, West Chester, Pennsylvania 19380, USA
2Center for the Study of Nervous System Injury, Dept. of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
3Geriatric Research Education and Clinical Center, Bedford Veterans Administration Medical Center, Bedford, Massachusetts, USA and the Neurology and Pathology Departments, Boston University School of Medicine, Boston, Massachusetts, USA
4Laboratory for Neurochemistry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
5Cecil B. Laboratory for Neuromuscular Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA The discovery that some cases of familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) has focused much attention on the function of SOD1 as related to motor neuron survival. Here we describe the creation and characterization of mice completely deficient for this enzyme. These animals develop normally and show no overt motor deficits by 6 months in age. Histological examination of the spinal cord reveals no signs of pathology in animals 4 months in age. However Cu/Zn SOD−deficient mice exhibit marked vulnerability to motor neuron loss after axonal injury. These results indicate that Cu/Zn SOD is not necessary for normal motor neuron development and function but is required under physiologically stressful conditions following injury.
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