Nishiyama K, Murayama S, Goto J, Watanabe M, Hashida H, Katayama S, Nomura Y, Nakamura S, Kanazawa I
Department of Neurology, Institute for Brain Research, School of Medicine, University of Tokyo, Japan.
Ann Neurol. 1996 Nov;40(5):776-81. doi: 10.1002/ana.410400514.
Machado-Joseph disease (MJD) is an autosomal dominant disorder characterized pathologically by spinocerebellar degeneration. Recently, an expansion of CAG repeat in a gene located at the chromosome 14q32.1 was found to be responsible for the disease. Here, we investigated in situ the expression of the MJD gene (MJD1) in the central nervous systems of normal and affected individuals and in rat brains. This gene was expressed in all regions of rat and human normal brains with certain regional variations. MJD1 was transcribed preferentially in neurons, although low levels of MJD1 mRNA were also observed in glial cells. Neurons susceptible to degeneration in MJD expressed MJD1 but not selectively. In the affected brains, the MJD1 mRNA distribution and amount in all the areas examined were similar in patients and controls. In addition, the cellular MJD1 mRNA level correlated neither with clinical severity nor expanded length. Our study showed that the expression levels of trinucleotide repeats in MJD patients and normal controls did not differ, indicating that the pathogenesis of MJD may involve direct toxicity to vulnerable subsets and/or region-specific cofactors of MJD proteins.
马查多-约瑟夫病（MJD）是一种常染色体显性疾病，其病理特征为脊髓小脑变性。最近发现，位于14号染色体q32.1区域的一个基因中的CAG重复序列扩增是导致该病的原因。在此，我们对正常个体及患病个体的中枢神经系统以及大鼠脑内MJD基因（MJD1）的原位表达进行了研究。该基因在大鼠和人类正常脑的所有区域均有表达，但存在一定的区域差异。MJD1主要在神经元中表达，不过在神经胶质细胞中也可观察到低水平的MJD1 mRNA。MJD中易发生变性的神经元表达MJD1，但并非选择性表达。在患病大脑中，所有检测区域的MJD1 mRNA分布及数量在患者和对照中相似。此外，细胞内MJD1 mRNA水平与临床严重程度及扩增长度均无关联。我们的研究表明，MJD患者和正常对照中三核苷酸重复序列的表达水平并无差异，这表明MJD的发病机制可能涉及对易感亚群和/或MJD蛋白区域特异性辅助因子的直接毒性作用。
