Development of central nervous system pathology in a murine transgenic model of human amyotrophic lateral sclerosis

M. C. Dal Canto*, M. E. Gurney

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

351 Scopus citations

Abstract

Transgenic mice expressing mutant Cu,Zn superoxide dismutase (SOD), containing a substitution of glycine at position 93 by alanine, develop disease prevalently affecting motor neurons. Light microscopical and ultrastructural studies reveal that the earliest pathological features are microvesiculation of large neurons of the anterior horns of the spinal cord. These vacuoles originate from dilation of rough endoplasmic reticulum and from degenerating mitochondria. At the end stage of the disease, the microvesicular pattern gives way to atrophic anterior horns showing severe neuronal depletion and hyaline, filamentous inclusions in some of the surviving neurons. Posterior horn neurons and dorsal root ganglia are not affected. With disease progression, moderate degeneration of anterior and lateral columns, severe degeneration of anterior roots, and mild degeneration in posterior columns and roots become apparent. This study shows that a mutation in SOD, known to occur in a percentage of familial amyotrophic lateral sclerosis patients, may affect only selective neuronal populations, although SOD is a ubiquitous enzyme.

Original languageEnglish (US)
Pages (from-to)1271-1279
Number of pages9
JournalAmerican Journal of Pathology
Volume145
Issue number6
StatePublished - 1994

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint

Dive into the research topics of 'Development of central nervous system pathology in a murine transgenic model of human amyotrophic lateral sclerosis'. Together they form a unique fingerprint.

Cite this