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Science 12 December 2003:
Vol. 302. no. 5652, pp. 1978 - 1980
DOI: 10.1126/science.1088583
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Reports

A Muscleblind Knockout Model for Myotonic Dystrophy

Rahul N. Kanadia,1 Karen A. Johnstone,1 Ami Mankodi,3 Codrin Lungu,3 Charles A. Thornton,3 Douglas Esson,2 Adrian M. Timmers,2 William W. Hauswirth,2 Maurice S. Swanson1*

The neuromuscular disease myotonic dystrophy (DM) is caused by microsatellite repeat expansions at two different genomic loci. Mutant DM transcripts are retained in the nucleus together with the muscleblind (Mbnl) proteins, and these abnormal RNAs somehow interfere with pre-mRNA splicing regulation. Here, we show that disruption of the mouse Mbnl1 gene leads to muscle, eye, and RNAsplicing abnormalities that are characteristic of DM disease. Our results support the hypothesis that manifestations of DM can result from sequestration of specific RNAbinding proteins by a repetitive element expansion in a mutant RNA.

1 Department of Molecular Genetics and Microbiology, Powell Gene Therapy Center, Gainesville, FL 32610, USA.
2 Department of Ophthalmology, University of Florida College of Medicine, Gainesville, FL 32610, USA.
3 Department of Neurology, Schoolof Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA.

* To whom correspondence should be addressed. E-mail: mswanson{at}ufl.edu

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