Li M, Miwa S, Kobayashi Y, Merry D E, Yamamoto M, Tanaka F, Doyu M, Hashizume Y, Fischbeck K H, Sobue G
Department of Neurology, Nagoya University School of Medicine, Japan.
Ann Neurol. 1998 Aug;44(2):249-54. doi: 10.1002/ana.410440216.
Spinal and bulbar muscular atrophy (SBMA) is an X-linked motor neuronopathy caused by the expansion of an unstable CAG repeat in the coding region of the androgen receptor (AR) gene. To study AR protein expression in normal and SBMA individuals, we used several antibodies that recognize AR protein, and analyzed neural and nonneural tissues by immunohistochemistry and western blotting. Both the normal and the mutant AR proteins were widely distributed, predominantly, but not exclusively, in the cytoplasm of neurons regardless of the pathological involvement, and predominantly in the nuclei of the nonneural tissues in both normal and SBMA individuals, with different expression levels of AR protein among different tissues. In the motor neurons of SBMA patients, there were AR-immunoreactive ubiquitinated nuclear inclusions that were detected by antibodies that recognize a small portion of the N terminus of the AR protein. Absence of other immunoreactive AR epitopes within the inclusion may be due to altered AR configuration, or masking of AR epitopes by other proteins, or proteolytic cleavage of the AR. Our data show that, in addition to the normal cellular distribution of the AR protein, mutant AR-bearing nuclear inclusions are present in SBMA.
脊髓延髓性肌萎缩症（SBMA）是一种X连锁运动神经元病，由雄激素受体（AR）基因编码区不稳定的CAG重复序列扩增引起。为了研究正常个体和SBMA患者体内AR蛋白的表达情况，我们使用了几种识别AR蛋白的抗体，并通过免疫组织化学和蛋白质印迹法分析了神经组织和非神经组织。无论病理情况如何，正常和突变的AR蛋白均广泛分布，主要但并非仅存在于神经元的细胞质中，在正常个体和SBMA患者的非神经组织细胞核中也主要存在，且不同组织中AR蛋白的表达水平不同。在SBMA患者的运动神经元中，存在AR免疫反应性泛素化核内包涵体，这些包涵体可被识别AR蛋白N端一小部分的抗体检测到。包涵体内其他免疫反应性AR表位的缺失可能是由于AR构象改变、AR表位被其他蛋白掩盖或AR发生蛋白水解切割所致。我们的数据表明，除了AR蛋白在细胞内的正常分布外，SBMA患者中还存在携带突变AR的核内包涵体。
