Restricted expression of G86R Cu/Zn superoxide dismutase in astrocytes results in astrocytosis but does not cause motoneuron degeneration

Yun H. Gong, Alexander S. Parsadanian, Albina Andreeva, William D. Snider, Jeffrey L. Elliott

Research output: Contribution to journalArticle

272 Scopus citations

Abstract

Evidence garnered from both human autopsy studies and genetic animal models has suggested a potential role for astrocytes in the pathogenesis of amyotrophic lateral sclerosis (ALS). Currently, mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) represent the only known cause of motoneuron loss in the disease, producing 21q linked familial ALS (FALS). To determine whether astrocytic dysfunction has a primary role in familial ALS, we have generated multiple lines of transgenic mice expressing G86R mutant SOD1 restricted to astrocytes. In GFAP-m SOD1 mice, astrocytes exhibit significant hypertrophy and increased GFAP reactivity as the animals mature. However, GFAP-mutant SOD1 transgenic mice develop normally and do not experience spontaneous motor deficits with increasing age. Histological examination of spinal cord in aged GFAP-mSOD1 mice reveals normal motoneuron and microglial morphology. These results indicate that 21q linked FALS is not a primary disorder of astrocytes, and that expression of mutant SOD1 restricted to astrocytes is not sufficient to cause motoneuron degeneration in vivo. Expression of mutant SOD1 in other cell types, most likely neurons, is critical for the initiation of disease.

Original languageEnglish (US)
Pages (from-to)660-665
Number of pages6
JournalJournal of Neuroscience
Volume20
Issue number2
DOIs
StatePublished - Jan 15 2000

Keywords

  • Amyotrophic lateral sclerosis
  • Glia
  • Gliosis
  • Glutamate
  • Mouse
  • Transgenic

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Restricted expression of G86R Cu/Zn superoxide dismutase in astrocytes results in astrocytosis but does not cause motoneuron degeneration'. Together they form a unique fingerprint.

  • Cite this