What transgenic mice tell us about neurodegenerative disease

Bioessays. 2000 Mar;22(3):297-304. doi: 10.1002/(SICI)1521-1878(200003)22:3<297::AID-BIES12>3.0.CO;2-I.


The recent broad advance in our understanding of human neurodegenerative diseases is based on the application of a new molecular approach. Through linkage analysis, the genes responsible for Huntington's disease, the spinocerebellar ataxias, and familial forms of Alzheimer's disease and amyotrophic lateral sclerosis (ALS) have been identified and cloned. The characterization of pathogenic mutations in such genes allows the creation of informative transgenic mouse models as, without exception, the genetic forms of adult neurodegenerative disease are due to toxicity of the mutant protein. Transgenic models provide insight into the oxidative mechanisms in ALS pathogenesis, the pathogenicity of expanded polyglutamine tracts in CAG triplet repeat disorders, and amyloidogenesis in Alzheimer's disease. Although such models have their limitations, they currently provide the best entry point for the study of human neurodegenerative diseases.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology
  • Animals
  • Humans
  • Mice
  • Mice, Transgenic*
  • Motor Neuron Disease / genetics
  • Motor Neuron Disease / physiopathology
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / physiopathology*
  • Trinucleotide Repeats