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

被引：369

作者：

Katsuno, M

Adachi, H

Kume, A

Li, M

Nakagomi, Y

Niwa, H

Sang, C

Kobayashi, Y

Doyu, M

Sobue, G

机构：

[1] Nagoya Univ, Grad Sch Med, Dept Neurol, Showa Ku, Nagoya, Aichi 4668550, Japan

[2] Aichi Med Univ, Electron Microscopy Lab, Nagakute, Aichi 4801195, Japan

来源：

NEURON | 2002年 / 35卷 / 05期

关键词：

D O I：

10.1016/S0896-6273(02)00834-6

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

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页码：843 / 854

页数：12

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