Testosterone reduction prevents phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy

Neuron. 2002 Aug 29;35(5):843-54. doi: 10.1016/s0896-6273(02)00834-6.


Spinal and bulbar muscular atrophy (SBMA) is a polyglutamine disease caused by the expansion of a CAG repeat in the androgen receptor (AR) gene. We generated a transgenic mouse model carrying a full-length AR containing 97 CAGs. Three of the five lines showed progressive muscular atrophy and weakness as well as diffuse nuclear staining and nuclear inclusions consisting of the mutant AR. These phenotypes were markedly pronounced in male transgenic mice, and dramatically rescued by castration. Female transgenic mice showed only a few manifestations that markedly deteriorated with testosterone administration. Nuclear translocation of the mutant AR by testosterone contributed to the phenotypic difference with gender and the effects of hormonal interventions. These results suggest the therapeutic potential of hormonal intervention for SBMA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Castration / statistics & numerical data
  • Chickens
  • Disease Models, Animal*
  • Female
  • Gene Expression / physiology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscular Atrophy, Spinal / genetics*
  • Muscular Atrophy, Spinal / metabolism*
  • Muscular Atrophy, Spinal / pathology
  • Phenotype
  • Receptors, Androgen / biosynthesis
  • Receptors, Androgen / genetics
  • Sex Characteristics
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Testosterone / biosynthesis
  • Testosterone / deficiency*
  • Testosterone / genetics*
  • Testosterone / physiology


  • Receptors, Androgen
  • Testosterone