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Myotonic Dystrophy in Transgenic Mice Expressing an Expanded CUG Repeat
Ami Mankodi,1Eric Logigian,1Linda Callahan,2Carolyn McClain,1Robert White,1Don Henderson,1Matt Krym,1Charles A. Thornton1*
Myotonic dystrophy (DM), the most common form of muscular dystrophy
in adult humans, results from expansion of a CTG repeatin the 3'
untranslated region of the DMPK gene. The mutant
DMPKmessenger RNA (mRNA) contains an expanded CUG repeat
and is retainedin the nucleus. We have expressed an untranslated CUG
repeat inan unrelated mRNA in transgenic mice. Mice that expressed
expandedCUG repeats developed myotonia and myopathy, whereas mice
expressinga nonexpanded repeat did not. Thus, transcripts with
expandedCUG repeats are sufficient to generate a DM phenotype. This
resultsupports a role for RNA gain of function in disease
pathogenesis.
1 Department of Neurology,
2 Department of Neurobiology and Anatomy, School of
Medicine and Dentistry, University of Rochester, Box 673, 601 Elmwood
Avenue, Rochester, NY 14642, USA.
*
To whom correspondence should be addressed. E-mail:
charles_thornton{at}urmc.rochester.edu
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