Myotonic dystrophy is a disorder that affects multiple body systems. It is characterized by progressive muscle weakness, cardiomyopathy and arrhythmias, cataracts, and abnormalities in brain and endocrine function, including mental retardation. There is a wide variation in the severity of symptoms between patients, although the condition is generally more severe and/or appears at an earlier age in later generations of a family that is affected. In a report in the current online issue of the Proceedings of the National Academy of Science, Professor Thomas Cooper and his colleagues from Baylor College of Medicine and France have shed further light on the molecular complexities of type 1 myotonic dystrophy (MMD1) and hinted at a possible reason for some of the differences between this disease and type 2 MMD (MMD2). The investigators describe how mice with expanded CUG repeats in the MMD1-associated gene on chromosome 19 (DMPK) have elevated levels of a protein called CUGBP1 in muscle cells and exhibit severe muscle wasting, as observed in humans with type 1 MMD. The increase in CUGBP1 levels, which has deleterious effects on muscle tissue and correlates with the severe muscle atrophy, appears to occur only when the expanded DNA sections are in the DMPK gene and not when they’re in other genes. People with MMD2, which involves an expansion of repeated DNA sequences in a gene other than DMPK, don’t have high levels of CUGBP1 and typically have milder muscle wasting than people with MMD1. The study challenges a widely held view that the location of the expanded DNA repeat isn’t important in either type of MMD and that its existence in any location would cause roughly the same problems.Unlike previous mouse models of the disease, these mice mimic the human disease better than any other mouse model of MMD1 created and have a genetic mutation that causes the muscle wasting that is the most devastating element of this inherited disorder.


Références : Proc Natl Acad Sci U S A. 2008 Feb 13; [Epub ahead of print]