Featured Research

from universities, journals, and other organizations

Study Offers New Insight Into Rett Syndrome

Date:
November 4, 2003
Source:
Whitehead Institute For Biomedical Research
Summary:
Rett Syndrome is a major cause of mental retardation in girls. Although researchers have identified the protein involved in the disease, its exact role remains a mystery. Now, a group of researchers from Children's Hospital Boston and Whitehead Institute of Biomedical Research have identified the protein's function, a discovery the scientists say could be the first significant advance in Rett Syndrome research in years.

Cambridge, Mass. – Rett Syndrome is a major cause of mental retardation in girls. Although researchers have identified the protein involved in the disease, its exact role remains a mystery. Now, a group of researchers from Children's Hospital Boston and Whitehead Institute of Biomedical Research have identified the protein's function, a discovery the scientists say could be the first significant advance in Rett Syndrome research in years.

The study, reported in this week's issue of the journal Science, describes how the protein in question controls gene expression in normal central nervous system cells. Researchers suspect that mutations in the protein impair its ability to regulate genes during a critical stage of brain development.

"We think that this deregulation may be responsible for some of the defects that we see in Rett patients," says Michael Greenberg, director of the Children's Hospital group and a lead author of the study.

A neurological disorder causing mental retardation as well as cerebral-palsy and autism-like symptoms, Rett Syndrome affects one out of approximately 15,000 female babies worldwide. Current therapies, including medications that help prevent seizures, treat some of the symptoms but not the disease.

Researchers have long known that mutations in a protein called MeCP2 somehow cause the disease, but until recently, little was known about how the protein worked. Previous lab experiments demonstrated that MeCP2 binds to genes that have undergone methylation (a fundamental biological process in which the cell disables genes it doesn't use by modifying them with methyl). Like a biological deadbolt, MeCP2 adheres to these methylated genes, further preventing them from ever activating. As a result, scientists theorized that MeCP2 was what they call a "long-range gene repressor."

Rudolf Jaenisch's Whitehead lab has studied this protein for years, demonstrating that when MeCP2 is disabled in mice, the animals manifest Rett-like symptoms. But they couldn't figure out why this happens, and they couldn't find the exact genes that MeCP2 targets.

At the same time, Greenberg, who also is a professor of neurobiology at Harvard Medical School, was studying a central nervous system gene that is highly active in infants age 6 to 18 months -- the same age that Rett symptoms first appear. Greenberg noted that this gene, called BDNF, constantly flips back and forth between an "on" state, where it rapidly produces protein, and an "off" state, during which it's silent.

"We knew a lot about how it was turned on," says Greenberg, "but we wanted to know what kept it off."

Greenberg and a graduate student in his laboratory Wen Chen discovered that the culprit behind the off state was MeCP2, suggesting that BDNF might also be a key player in Rett Syndrome. The Greenberg and Jaenisch labs began collaborating to learn how these two molecules interacted. Jaenisch's lab supplied mouse neuron cells, and Greenberg's group provided similar cells taken from rats.

Everything researchers knew about MeCP2 led the team to expect that once the protein bound to BDNF, the gene would become permanently inactive, and MeCP2 would ensure that BDNF remained silent throughout the cell's life. Instead, they discovered a far more dynamic process.

After the BDNF gene is methylated, MeCP2 does indeed bind to it, shutting the gene off -- but only temporarily. If the neuron cells are excited by any kind of environmental stimulus, MeCP2 immediately detaches, and the BDNF gene begins producing protein. When the stimulus disappears, MeCP2 re-attaches to BDNF, again locking the deadbolt until a neuronal stimulus starts the process again. Greenberg and Jaenisch say they have never before witnessed this kind of process.

"I find this to be an extremely exciting new development," says Adrian Bird, professor of genetics at Edinburgh University in Scotland, whose lab discovered MeCP2 more than a decade ago. "To me, what's particularly surprising is that you have DNA methylation involved with dynamic regulation of the gene."

Still, Bird, who also is chair of the scientific advisory board for the Rett Syndrome Research Foundation, which, along with the National Institutes of Health, funded this study, is cautious about over interpreting the results. "It might well be that BDNF is a crucial gene that explains some of the symptoms of Rett patients. But we can't be really sure yet."

One theory this study suggests is that in Rett patients, mutations in MeCP2 impair its ability to regulate BDNF, and that BDNF's subsequent over-expression may cause Rett. However, Greenberg points out that BDNF is only one of approximately 300 genes that are controlled by neuronal activity, many of which also may be targeted by MeCP2.

"BDNF is probably not the key gene in Rett Syndrome," Jaenisch says. "More likely, it's one of many genes."

The next step, says Greenberg, "is to identify other genes that are regulated by MeCP2," which he says now can be done on a genome-wide scale.


Story Source:

The above story is based on materials provided by Whitehead Institute For Biomedical Research. Note: Materials may be edited for content and length.


Cite This Page:

Whitehead Institute For Biomedical Research. "Study Offers New Insight Into Rett Syndrome." ScienceDaily. ScienceDaily, 4 November 2003. <www.sciencedaily.com/releases/2003/11/031104063414.htm>.
Whitehead Institute For Biomedical Research. (2003, November 4). Study Offers New Insight Into Rett Syndrome. ScienceDaily. Retrieved September 19, 2014 from www.sciencedaily.com/releases/2003/11/031104063414.htm
Whitehead Institute For Biomedical Research. "Study Offers New Insight Into Rett Syndrome." ScienceDaily. www.sciencedaily.com/releases/2003/11/031104063414.htm (accessed September 19, 2014).

Share This



More Mind & Brain News

Friday, September 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Food Addiction Might Be Caused By PTSD

Food Addiction Might Be Caused By PTSD

Newsy (Sep. 18, 2014) New research shows that women who suffer from PTSD are three times more likely to develop a food addiction. Video provided by Newsy
Powered by NewsLook.com
Corporal Punishment on Decline, Debate Renews

Corporal Punishment on Decline, Debate Renews

AP (Sep. 16, 2014) Corporal punishment in the United States is on the decline, but there is renewed debate over its use after Minnesota Vikings running back Adrian Peterson was charged with child abuse. (Sept. 16) Video provided by AP
Powered by NewsLook.com
FDA Eyes Skin Shocks Used at Mass. School

FDA Eyes Skin Shocks Used at Mass. School

AP (Sep. 15, 2014) The FDA is considering whether to ban devices used by the Judge Rotenberg Educational Center in Canton, Massachusetts, the only place in the country known to use electrical skin shocks as aversive conditioning for aggressive patients. (Sept. 15) Video provided by AP
Powered by NewsLook.com
Shocker: Journalists Are Utterly Addicted To Coffee

Shocker: Journalists Are Utterly Addicted To Coffee

Newsy (Sep. 13, 2014) A U.K. survey found that journalists consumed the most amount of coffee, but that's only the tip of the coffee-related statistics iceberg. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins