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Scientists create first animal model of Rett Syndrome

Researchers from the Whitehead Institute for Biomedical Research have created the long-awaited animal model for Rett syndrome, one of the most common causes of mental retardation in females with an incidence of 1 in 10,000-15,000. The transgenic mouse model sheds much-needed light on the underlying mechanism of the disease and suggests a new reason for hope in the research toward therapies.

Rett syndrome, caused by a defective gene on the X-chromosome, is thought to have a lethal effect in males before birth or shortly after. Girls with Rett syndrome (and two copies of the X chromosome) are healthy babies who develop normally until six to eighteen months old. But then something goes terribly wrongtheir health deteriorates and they begin to show symptoms such as loss of speech, loss of voluntary motor control, constant hand wringing, and seizures.

The work, published in the March 2001 issue of Nature Genetics from Rudolf Jaenisch and colleagues, suggests that the genetic defect underlying Rett syndrome has an effect not only during brain development before birth but has critical prolonged effects even after birth. Since it is easier to treat newborns than to correct defects in embryonic development, these findings may hold promise for future therapies.

In 1999, scientists from the Baylor College of Medicine in Houston, Texas, found that mutations in a gene called MECP2 were responsible for Rett syndrome. However, the exact mechanism by which mutated MECP2 brings about the mental deterioration was unknown.

The Jaenisch lab was able to use its expertise in transgenic technology to create mice in which the Mecp2 gene could be disrupted at any time during their development before or after birth. To the researchers surprise, male mice lacking Mecp2 did not die and showed a less severe syndrome. The male mice developed Rett-like symptoms, but survived to young adulthood, and females remained healthy well into adulthood. Similarities between the bra
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Contact: Nadia Halim
halim@wi.mit.edu
617-258-7270
Whitehead Institute for Biomedical Research
1-Mar-2001


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