This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Flood, D. G. Articles by Scott, R. W. Search for Related Content PubMed PubMed Citation Articles by Flood, D. G. Articles by Scott, R. W.

(American Journal of Pathology. 1999;155:663-672.)
© 1999 American Society for Investigative Pathology

Animal Model

Hindlimb Motor Neurons Require Cu/Zn Superoxide Dismutase for Maintenance of Neuromuscular Junctions

Dorothy G. Flood^*, Andrew G. Reaume^*, John A. Gruner, Eric K. Hoffman^*, James D. Hirsch^*, Yin-Guo Lin^*, Karen S. Dorfman^* and Richard W. Scott^*

From the Departments of Molecular Biology^*
and Pharmacology,
Cephalon, Inc., West Chester, Pennsylvania

The role of oxidative damage in neurodegenerative disease was investigated in mice lacking cytoplasmic Cu/Zn superoxide dismutase (SOD), created by deletion of the SOD1 gene (SOD1^-/-). SOD1^-/- mice developed a chronic peripheral hindlimb axonopathy. Mild denervation of muscle was detected at 2 months, and behavioral and physiological motor deficits were present at 5–7 months of age. Ventral root axons were shrunken but were normal in number. The somatosensory system in SOD1^-/- mice was mildly affected. SOD1^-/- mice expressing Cu/Zn SOD only in brain and spinal cord were generated using transgenic mice expressing mouse SOD1 driven by the neuron-specific synapsin promoter. Neuron-specific expression of Cu/Zn SOD in SOD1^-/- mice rescued motor neurons from the neuropathy. Therefore, Cu/Zn SOD is not required for normal motor neuron survival, but is necessary for the maintenance of normal neuromuscular junctions by hindlimb motor neurons.

This article has been cited by other articles:

				A. Bhattacharya, F. L. Muller, Y. Liu, M. Sabia, H. Liang, W. Song, Y. C. Jang, Q. Ran, and H. Van Remmen Denervation Induces Cytosolic Phospholipase A2-mediated Fatty Acid Hydroperoxide Generation by Muscle Mitochondria J. Biol. Chem., January 2, 2009; 284(1): 46 - 55. [Abstract] [Full Text] [PDF]

				F. L. Muller, W. Song, Y. C. Jang, Y. Liu, M. Sabia, A. Richardson, and H. Van Remmen Denervation-induced skeletal muscle atrophy is associated with increased mitochondrial ROS production Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1159 - R1168. [Abstract] [Full Text] [PDF]

				H. Tummala, C. Jung, A. Tiwari, C. M. J. Higgins, L. J. Hayward, and Z. Xu Inhibition of Chaperone Activity Is a Shared Property of Several Cu,Zn-Superoxide Dismutase Mutants That Cause Amyotrophic Lateral Sclerosis J. Biol. Chem., May 6, 2005; 280(18): 17725 - 17731. [Abstract] [Full Text] [PDF]

				L. Vila, E. F Barrett, and J. N Barrett Stimulation-induced mitochondrial [Ca2+] elevations in mouse motor terminals: comparison of wild-type with SOD1-G93A J. Physiol., June 15, 2003; 549(3): 719 - 728. [Abstract] [Full Text] [PDF]

				Copper, Zinc Superoxide Dismutase Sci. Aging Knowl. Environ., October 31, 2001; 2001(5): tg15 - 15. [Full Text]

				S. Hadjur, K. Ung, L. Wadsworth, J. Dimmick, E. Rajcan-Separovic, R. W. Scott, M. Buchwald, and F. R. Jirik Defective hematopoiesis and hepatic steatosis in mice with combined deficiencies of the genes encoding Fancc and Cu/Zn superoxide dismutase Blood, August 15, 2001; 98(4): 1003 - 1011. [Abstract] [Full Text] [PDF]