Mouse Model Suggests Treatment Strategy For Muscular Dystrophy

Myotonic dystrophy occurs because of a large expansion in the number of 'CTG' repeats in a region flanking a gene called DMPK, and is associated with skeletal muscle loss, cardiac abnormalities, cataracts and insulin resistance. While there has been good evidence in favor of the idea that the expanded DMPK messenger RNA is toxic to cells in which it is expressed, and is the underlying cause of the disease, a definitive demonstration has been lacking. Mani Mahadevan and colleagues at the University of Virginia generated a mouse carrying an extra normal copy of the DMPK gene that could be turned on and off by adding (or removing) an antibiotic to the drinking water. Mice that expressed very high levels of this extra DMPK -- and thus had more copies of the CTG repeat -- showed all of the cardinal features of myotonic dystrophy. When expression of DMPK was turned off, normal skeletal and cardiac muscle function was restored in many of the mice. These results suggest that muscle damage in individuals with the disease might not be permanent, and that eliminating messenger RNAs carrying the extra CTG repeats might have therapeutic benefit.

Author contacts:

Mani Mahadevan (University of Virginia, Charlottesville, USA)
E-mail: mahadevan@virginia.edu

Ramesh Yadava (University of Virginia, Charlottesville, USA)
E-mail: ry3b@virginia.edu

Additional contact for comment on paper:

Lubov Timchenko (Baylor College of Medicine, Houston, TX, USA)
E-mail: lubovt@bcm.tmc.edu

Abstract available online.

(C) Nature Genetics press release.

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