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Introduction of the 'Rett protein' in post-mitotic neurons rescues Rett Syndrome in mice

Rudolf Jaenisch of the Whitehead Institute of Biomedical Research in Cambridge, MA reports in the April 6, 2004 online issue of the Proceedings of the National Academy of Sciences that introduction of the MeCP2 protein into post-mitotic nerve cells of MeCP2 mutant mice rescues the symptoms of Rett Syndrome. This raises the possibility that neurons are functionally normal in a newborn child and that neural dysfunction manifests itself only later due to prolonged MeCP2 deficiency. If correct, therapeutic strategies aimed at preventing the onset of Rett symptoms could be initiated at birth. This project was funded by the Rett Syndrome Research Foundation (RSRF) and the National Institutes of Health (NIH).

Rett Syndrome (RTT) is a severe neurological disorder diagnosed almost exclusively in girls. Children with RTT appear to develop normally until 6 to 18 months of age, when they enter a period of regression, losing speech and motor skills. Most develop repetitive hand movements, irregular breathing patterns, seizures and extreme motor control problems. RTT leaves its victims profoundly disabled, requiring maximum assistance with every aspect of daily living. There is no cure.

In late 1999 it was discovered that mutations in the gene MECP2 were the leading cause of Rett Syndrome. The gene product, MeCP2, is a protein believed to play a vital role in the regulation of gene expression. It is expressed in all organs and found in especially high levels in the brain. The timing of MeCP2 activation coincides with the maturation of the central nervous system and recent reports suggest that MeCP2 may be involved in the formation of contacts between nerve cells and may function in activity-dependent gene expression (i.e. learning). Multiple labs have shown that selective mutation of MeCP2 in nerve cells after birth leads to Rett-like symptoms in mice, suggesting that MeCP2 plays an important role in mature nerve cells.

Dr. Jaenisch devised an expe
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Contact: Monica Coenraads
monica@rsrf.org
203-445-9233
Rett Syndrome Research Foundation
7-Apr-2004


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