Katsuno Masahisa, Adachi Hiroaki, Kume Akito, Li Mei, Nakagomi Yuji, Niwa Hisayoshi, Sang Chen, Kobayashi Yasushi, Doyu Manabu, Sobue Gen
Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan.
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.
脊髓和延髓性肌萎缩症（SBMA）是一种由雄激素受体（AR）基因中CAG重复序列扩增引起的多聚谷氨酰胺疾病。我们构建了一个携带含有97个CAG的全长AR的转基因小鼠模型。五个品系中的三个表现出进行性肌肉萎缩和无力，以及由突变型AR组成的弥漫性核染色和核内包涵体。这些表型在雄性转基因小鼠中明显更显著，并通过去势得到显著改善。雌性转基因小鼠仅表现出少数随着睾酮给药而明显恶化的表现。睾酮导致的突变型AR核转位导致了性别间的表型差异以及激素干预的效果。这些结果提示了激素干预对SBMA的治疗潜力。
