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Researchers trace effects of genetic defect in myotonic muscular dystrophy
Date:1/24/2010

ected hundreds of splicing events that were being affected, giving us a broader picture of what's going on in cells as the disease is taking hold," Ares said.

Tests for some of the newly identified splicing defects in human patients with myotonic dystrophy confirmed that the same changes occur in both mouse and human cells. More extensive testing in humans will enable the researchers to identify which RNA splicing changes might be clinically useful for diagnosing or monitoring the disease, Ares said.

The researchers also found another set of changes that were seen only in the mouse strain that makes the abnormal repeat RNA and not in the mice lacking Mbnl1. These effects were not splicing errors, but changes in gene expression detected by microarrays that measured the amounts of messenger RNA being transcribed from different genes.

"We suspect that the loss of Mbnl2 is responsible for those gene expression defects," Ares said.

Many of the genes with altered expression levels are involved in making the extracellular matrix, a protein coat that binds muscle cells together and enables muscle tissue to generate a coherent force when it contracts.

"We're excited by this finding because the group of genes affected is rich in these structural components operating outside the cell to hold the tissue together, and that might explain some aspects of the disease," Ares said. "Some of the genes in this class have been implicated in other kinds of genetically inherited muscular dystrophy and connective tissue diseases, revealing unanticipated links with the myotonic form of muscular dystrophy."

A recent grant from the Muscular Dystrophy Association will enable Ares and his collaborators to investigate how these findings might be used to help patients with myotonic dystrophy. The researchers may be able to develop methods for early detection of the disease or for predicting how the disease will progress in individual patient
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Contact: Tim Stephens
stephens@ucsc.edu
831-459-2495
University of California - Santa Cruz
Source:Eurekalert

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