Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat

Myotonic dystrophy (DM), the most common form of muscular dystrophy in adul t humans, results from expansion of a CTC repeat in the 3' untranslated reg ion of the DMPK gene. The mutant DMPK messenger RNA (mRNA) contains an expa nded CUG repeat and is retained in the nucleus. We have expressed an untran slated CUG repeat in an unrelated mRNA in transgenic mice. Mice that expres sed expanded CUG repeats developed myotonia and myopathy, whereas mice expr essing a nonexpanded repeat did not, Thus, transcripts with expanded CUG re peats are sufficient to generate a DM phenotype. This result supports a rol e for RNA gain of function in disease pathogenesis.