Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers alleviate symptoms of Rett syndrome in mice

02.02.2006


Rett syndrome is a debilitating neurological disorder occurring primarily in girls. While some existing therapies might ease particular symptoms of the condition, there is no current way to address the syndrome at a molecular level. Now, researchers at Whitehead Institute for Biomedical Research, in collaboration with scientists at Brandeis University, have dramatically reduced certain manifestations of Rett Syndrome in mice, marking a clear path in which to explore possible therapies for people.



"This is the first time we’ve successfully reduced the awful symptoms of Rett syndrome using transgenic techniques," says Whitehead Member Rudolf Jaenisch, senior author of the paper that will be published February 2 in the journal Neuron. "Once we understand the molecular mechanisms of the disease we may be able to design rational strategies that may eventually be useful for the improving the condition in people."

Rett syndrome, whose incidence is roughly 1 in 15,000, is caused by a defective gene on the X chromosome. Most boys with Rett syndrome die before birth. Girls with Rett develop normally until about six to eighteen months, when things begin to go terribly wrong. Their health deteriorates, and they begin to show symptoms such as loss of speech, loss of voluntary motor control, constant hand wringing and seizures.


In March 2001, researchers in the Jaenisch lab published a paper in Nature Genetics describing how they had created the first mouse with Rett syndrome by disabling a gene called MeCP2. Normally, MeCP2 regulates the activities of other genes, particularly those in the brain. When it is shut off completely, the mice become lethargic and a major class of cortical neurons became far less active--classic symptoms of Rett.

In the fall of 2003, Jaenisch and researchers at Children’s Hospital Boston reported in the journal Science that MeCP2 interacted with a neuronal gene called Bdnf, a gene that’s highly active in infants age 6 to 18 months--the same age at which Rett symptoms first appear. But since this study was conducted using explanted neurons in a laboratory dish, researchers still had many unanswered questions about the role of Bdnf in Rett disease progression in mice.

Qiang Chang, a postdoctoral scientist in the Jaenisch lab, began to explore this issue by studying the population of the MeCP2 knock-out mice that Jaenisch had reported on in 2001. His first finding, gleaned through analyzing brain tissue, was not altogether unexpected: Mice without MeCP2 also showed low expression levels of the BDNF protein. In fact, Chang discovered that when he knocked out Bdnf altogether in normal mice, symptoms similar to those observed in the Rett mice occurred. But to discover whether or not these finding might have therapeutic relevance, Chang needed to engage in some complex genetic tinkering.

Chang inserted an additional Bdnf gene into the early embryos of the MeCP2 knock-out mice. He designed the gene so that it would be free of all normal regulatory mechanisms, in effect ensuring that it remains in a state of constant activity. In other words, while MeCP2 was permanently shut off, the new Bdnf was permanently switched on, and at maximum capacity.

This time, the findings were striking.

With BDNF hyper-expressed, Chang witnessed a drastic reduction in certain Rett symptoms. The mice were far less lethargic, and activity in the cortical neurons increased. These mice also had slightly larger brains, a longer lifespan and later onset of disease than the other Rett mice.

"The next step," says Chang, "is to figure out exactly why this is happening. Exactly how much BDNF expression in the mouse brain do you need to achieve these results, and where does it occur?"

"Knowing more about the process and about the precise areas of the brain that are affected will give us options for exploring future therapies," explains Jaenisch, who is also a professor of biology at MIT.

"We’re encouraged by these results," says Monica Coenraads, co-founder and director of research for Rett Syndrome Research Foundation, who helped support this work. "Should this prove to be therapeutically relevant, we look forward to participating in the transition from lab to clinic."

David Cameron | EurekAlert!
Further information:
http://www.wi.mit.edu

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>