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1: Science. 2003 Dec 12;302(5652):1978-80.Click here to read Links

A muscleblind knockout model for myotonic dystrophy.

Kanadia RN, Johnstone KA, Mankodi A, Lungu C, Thornton CA, Esson D, Timmers AM, Hauswirth WW, Swanson MS.

Department of Molecular Genetics and Microbiology, Powell Gene Therapy Center, Gainesville, FL 32610, USA.

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 RNA splicing abnormalities that are characteristic of DM disease. Our results support the hypothesis that manifestations of DM can result from sequestration of specific RNA binding proteins by a repetitive element expansion in a mutant RNA.

PMID: 14671308 [PubMed - indexed for MEDLINE]