Axonal transport of mutant superoxide dismutase 1 and focal axonal abnormalities in the proximal axons of transgenic mice

David R. Borchelt, Philip C. Wong, Mark W. Becher, Carlos A. Pardo, Michael K. Lee, Zuo Shang Xu, Gopal Thinakaran, Nancy A. Jenkins, Neal G. Copeland, Sangram S. Sisodia, Don W. Cleveland, Donald L. Price, Paul N. Hoffman

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91 Scopus citations


Superoxide dismutase 1 (SOD1), a ubiquitously expressed enzyme, detoxifies superoxide radicals and participates in copper homeostasis. Mutations in this enzyme have been linked to a subset of autosomal dominant cases of familial amyotrophic lateral sclerosis (FALS), a disorder characterized by selective degeneration of motor neurons. Transgenic mice expressing FALS mutant human (Hu) SOD1 at high levels develop a motor neuron disease, indicating that mutant HU SOD1 gains properties that are particularly toxic to motor neurons. In this report, we demonstrate that transgenic mice expressing Hu SOD1 with the G37R FALS mutation, but not mice expressing wild-type enzyme, develop focal increases in immunoreactivity in the proximal axons of spinal motor neurons. This SOD1 immunoreactivity and immunoreactivity to hypophosphorylated neurofilament H epitopes are found adjacent to small vacuoles in axons. Using metabolic radiolabeling methods, we show that mutant G37R HuSOD1 as well as endogenous mouse SOD1 are transported anterograde in slow component b in motor and sensory axons of the sciatic nerve. Together, these findings suggest that anterogradely transported mutant SOD1 may act locally to damage motor axons.

Original languageEnglish (US)
Pages (from-to)27-35
Number of pages9
JournalNeurobiology of Disease
Issue number1
StatePublished - Jul 1998

Bibliographical note

Funding Information:
The authors thank Drs. Jeffrey Rothstein, Lucie Bruijn, and Valeria Culotta for helpful discussions and Ms. Marilyn Peper for excellent technical assistance. This work was supported by grants from the NIH: NS 27036 (DWC, Z-SX), NS 32724 (PNH), NS 01719, AG 05146, and NS 20471. We also acknowledge grants from the Amyotrophic Lateral Sclerosis Association (D.R.B., P.C.W., M.K.L.), the Metropolitan Life Foundation, and the Cal Ripken/Lou Gehrig Fund for ALS Research. Drs. Price, Borchelt, and Wong are the recipients of a Leadership and Excellence in Alzheimer’s Disease (LEAD) award from the NIH (AG 07914); Dr. Price is the recipient of a Javits Neuroscience Investigator Award from the NIH (NS 10580).


  • Axonal transport
  • Familial amyotrophic lateral sclerosis
  • Mutant
  • Slow component b
  • Superoxide dismutase 1


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