Bcl-2: prolonging life in a transgenic mouse model of familial amyotrophic lateral sclerosis

Science. 1997 Jul 25;277(5325):559-62. doi: 10.1126/science.277.5325.559.

Abstract

Mutations in the gene encoding copper/zinc superoxide dismutase enzyme produce an animal model of familial amyotrophic lateral sclerosis (FALS), a fatal disorder characterized by paralysis. Overexpression of the proto-oncogene bcl-2 delayed onset of motor neuron disease and prolonged survival in transgenic mice expressing the FALS-linked mutation in which glycine is substituted by alanine at position 93. It did not, however, alter the duration of the disease. Overexpression of bcl-2 also attenuated the magnitude of spinal cord motor neuron degeneration in the FALS-transgenic mice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / mortality
  • Amyotrophic Lateral Sclerosis / pathology
  • Amyotrophic Lateral Sclerosis / therapy*
  • Animals
  • Disease Models, Animal
  • Female
  • Gene Expression*
  • Genes, bcl-2*
  • Genetic Therapy*
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Motor Neurons / pathology
  • Nerve Degeneration
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Proto-Oncogene Proteins c-jun / analysis
  • Spinal Cord / pathology
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Survival Rate
  • Ubiquitins / analysis

Substances

  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-jun
  • Ubiquitins
  • Superoxide Dismutase