Takahashi N, Ishiura S
Department of Molecular Biology, University of Tokyo.
Nihon Rinsho. 1999 Apr;57(4):937-42.
Although the expansion of an unstable CTG repeat is known to be responsible for myotonic dystrophy (DM), the mechanism by which this genetic defect induces the disease has not yet been elucidated. In patients with DM, low expression of total DM protein kinase (DMPK) and equal expression of each allele were confirmed. These result suggest that the gene product of expanded allele of DMPK causes a cis- and trans-effect on DMPK or other genes. On the other hand, existence of CUG repeat binding proteins (BP) in the nucleus of cells were reported. These CUG-BP complex may form an aggregation in the nucleus, which probably works as an inhibitory factor for the nuclear cytoplasmic transport of mRNA. All of these considerations reveal the gain-of-function model of DM, but still leave room for many more question to be answer.
尽管已知不稳定的CTG重复序列扩增是强直性肌营养不良（DM）的病因，但这种基因缺陷导致疾病的机制尚未阐明。在DM患者中，已证实总DM蛋白激酶（DMPK）表达降低且每个等位基因表达相等。这些结果表明，DMPK扩增等位基因的基因产物对DMPK或其他基因产生顺式和反式效应。另一方面，有报道称细胞细胞核中存在CUG重复结合蛋白（BP）。这些CUG-BP复合物可能在细胞核中形成聚集体，这可能作为mRNA核质转运的抑制因子。所有这些推测揭示了DM的功能获得模型，但仍有许多问题有待解答。
