| RRC ID |
2385
|
| Author |
Katsuno M, Adachi H, Kume A, Li M, Nakagomi Y, Niwa H, Sang C, Kobayashi Y, Doyu M, Sobue G.
|
| Title |
Testosterone reduction prevents phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy.
|
| Journal |
Neuron
|
| Abstract |
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.
|
| Volume |
35(5)
|
| Pages |
843-54
|
| Published |
2002-8-29
|
| DOI |
10.1016/s0896-6273(02)00834-6
|
| PII |
S0896627302008346
|
| PMID |
12372280
|
| MeSH |
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
|
| IF |
14.415
|
| Times Cited |
321
|
|
WOS Category
|
NEUROSCIENCES
|
| Resource |
| Mice |
RBRC00344
RBRC00373 |
