Disease mechanisms revealed by transcription profiling in SOD1-G93A transgenic mouse spinal cord.


Journal Article

Mutations of copper,zinc-superoxide dismutase (cu,zn SOD) are found in patients with a familial form of amyotrophic lateral sclerosis. When expressed in transgenic mice, mutant human cu,zn SOD causes progressive loss of motor neurons with consequent paralysis and death. Expression profiling of gene expression in SOD1-G93A transgenic mouse spinal cords indicates extensive glial activation coincident with the onset of paralysis at 3 months of age. This is followed by activation of genes involved in metal ion regulation (metallothionein-I, metallothionein-III, ferritin-H, and ferritin-L) at 4 months of age just prior to end-stage disease, perhaps as an adaptive response to the mitochondrial destruction caused by the mutant protein. Induction of ferritin-H and -L gene expression may also limit iron catalyzed hydroxyl radical formation and consequent oxidative damage to lipids, proteins, and nucleic acids. Thus, glial activation and adaptive responses to metal ion dysregulation are features of disease in this transgenic model of familial amyotrophic lateral sclerosis.

Full Text

Cited Authors

  • Olsen, MK; Roberds, SL; Ellerbrock, BR; Fleck, TJ; McKinley, DK; Gurney, ME

Published Date

  • December 2001

Published In

Volume / Issue

  • 50 / 6

Start / End Page

  • 730 - 740

PubMed ID

  • 11761470

Pubmed Central ID

  • 11761470

Electronic International Standard Serial Number (EISSN)

  • 1531-8249

International Standard Serial Number (ISSN)

  • 0364-5134

Digital Object Identifier (DOI)

  • 10.1002/ana.1252


  • eng