A Muscleblind Knockout Model for Myotonic Dystrophy

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Science  12 Dec 2003:
Vol. 302, Issue 5652, pp. 1978-1980
DOI: 10.1126/science.1088583

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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.

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