Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

2 genes affect anxiety, behavior in mice with too much MeCP2

09.01.2012
The anxiety and behavioral issues associated with excess MeCP2 protein result from overexpression of two genes (Crh [corticotropin-releasing hormone] and Oprm 1 [mu-opioid receptor MOR 1]), which may point the way to treating these problems in patients with too much of the protein, said Baylor College of Medicine scientists in a report that appears online in the journal Nature Genetics.

Much of the work was done at the Jan and Dan L. Duncan Neurological Research Institute at Texas Children's Hospital.

MeCP2 is a "Goldilocks" in the protein world. When the protein is lacking or defective, girls develop the neurological disorder Rett syndrome early in life. Too much protein results in the more recently identified MeCP2 duplication syndrome, which usually affects boys, who may inherit the gene duplications either from their mothers or, in rare cases, develop it sporadically. In both cases, anxiety and social behavioral deficits are typical of those with the disease, along with other motor problems and cognitive defects.

"This is a nice example of a translational story," said Dr. Rodney Samaco, assistant professor of molecular and human genetics at BCM and first author of the paper. "We first identified the mouse model for MeCP2 duplication syndrome and then found people with the disorder in the clinic. We went back to the lab and found out that MeCP2 was indeed the major contributor to this phenotype in patients. We have now identified two genes involved in two major symptoms of the syndrome. Eventually, we may take the information back to the clinic to develop a treatment for patients."

"Loss or Gain of MeCP2 affects the expression of hundreds of genes, but discovering that two genes are the culprits in mediating anxiety and social behavioral problems is surprising," said Dr. Huda Zoghbi, professor of molecular and human genetics, neurology, neuroscience, and pediatrics at BCM and director of the NRI. She is the corresponding author of the report and a Howard Hughes Medical Institute Investigator.

Patients with MeCP2 duplication disorder have a duplication in chromosomes that span both the MECP2 gene and another called IRAK1. But with this new study, it is now clear that excess MeCP2 accounts for the neuropsychiatric symptoms.

In mice, doubled MeCP2 levels caused both anxiety and autism-like behaviors and altered the expression of several hundred genes. Of these, two genes – Crh and Oprm1, are implicated in anxiety and social behavior, said Samaco.

"Then, when we reduced the levels of Crh, we saw reduced anxiety," he said. "When we reduced levels of Oprm1, we improved the social behavior problems."

This finding is important because it shows that tweaking the expression of genes that the protein affects, rather than trying to adjust the levels of the finicky MeCP2 protein itself, can modify symptoms of MeCP2 disorders.

In fact, Samaco also reduced levels of the protein that is a cellular receptor for Crh, both through molecular means and with the use of a drug, and found that anxiety levels also went down. That could provide another means of dealing with anxiety associated with the duplication syndrome.

Others who took part in this research include: Caleigh Mandel-Brehm, Christopher M. McGraw, Chad A. Shaw and Bryan E. McGill, all with BCM when the research was done.

Support and funding for this work came from the BCM Intellectual and Developmental Disabilities Research Center, the BCM Microarray Core and the RNA In Situ and Mouse Neurobehavior cores at BCM, the National Institutes of Health, Autism Speaks, the Carl C. Anderson Sr. and Marie Jo Anderson Charitable Foundation, the Simons Foundation, the Rett Syndrome Research Trust, and the Howard Hughes Medical Institute.

For more information on basic science research at Baylor College of Medicine, please go to From the Lab at BCM.

Graciela Gutierrez | EurekAlert!
Further information:
http://www.bcm.edu

More articles from Life Sciences:

nachricht First use of vasoprotective antibody in cardiogenic shock
17.05.2019 | Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.

nachricht A nerve cell serves as a “single” for studies
15.05.2019 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Self-repairing batteries

UTokyo engineers develop a way to create high-capacity long-life batteries

Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...

Im Focus: Quantum Cloud Computing with Self-Check

With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.

Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...

Im Focus: Accelerating quantum technologies with materials processing at the atomic scale

'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.

However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...

Im Focus: A step towards probabilistic computing

Working group led by physicist Professor Ulrich Nowak at the University of Konstanz, in collaboration with a team of physicists from Johannes Gutenberg University Mainz, demonstrates how skyrmions can be used for the computer concepts of the future

When it comes to performing a calculation destined to arrive at an exact result, humans are hopelessly inferior to the computer. In other areas, humans are...

Im Focus: Recording embryonic development

Scientists develop a molecular recording tool that enables in vivo lineage tracing of embryonic cells

The beginning of new life starts with a fascinating process: A single cell gives rise to progenitor cells that eventually differentiate into the three germ...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

Discovering unusual structures from exception using big data and machine learning techniques

17.05.2019 | Materials Sciences

ALMA discovers aluminum around young star

17.05.2019 | Physics and Astronomy

A new iron-based superconductor stabilized by inter-block charger transfer

17.05.2019 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>