Mankodi A, Logigian E, Callahan L, McClain C, White R, Henderson D, Krym M, Thornton C A
Department of Neurology, School of Medicine and Dentistry, University of Rochester, Box 673, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Science. 2000 Sep 8;289(5485):1769-73. doi: 10.1126/science.289.5485.1769.
Myotonic dystrophy (DM), the most common form of muscular dystrophy in adult humans, results from expansion of a CTG repeat in the 3' untranslated region of the DMPK gene. The mutant DMPK messenger RNA (mRNA) contains an expanded CUG repeat and is retained in the nucleus. We have expressed an untranslated CUG repeat in an unrelated mRNA in transgenic mice. Mice that expressed expanded CUG repeats developed myotonia and myopathy, whereas mice expressing a nonexpanded repeat did not. Thus, transcripts with expanded CUG repeats are sufficient to generate a DM phenotype. This result supports a role for RNA gain of function in disease pathogenesis.
强直性肌营养不良（DM）是成年人类中最常见的肌营养不良形式，由DMPK基因3'非翻译区的CTG重复序列扩增引起。突变的DMPK信使核糖核酸（mRNA）含有扩增的CUG重复序列，并保留在细胞核中。我们在转基因小鼠的无关mRNA中表达了未翻译的CUG重复序列。表达扩增CUG重复序列的小鼠出现了肌强直和肌病，而表达未扩增重复序列的小鼠则没有。因此，具有扩增CUG重复序列的转录本足以产生DM表型。这一结果支持了RNA功能获得在疾病发病机制中的作用。
