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 New photocatalyst speeds up the conversion of carbon dioxide into chemical resources
29.05.2017 | DGIST (Daegu Gyeongbuk Institute of Science and Technology)

nachricht Copper hydroxide nanoparticles provide protection against toxic oxygen radicals in cigarette smoke
29.05.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

New insights into the ancestors of all complex life

29.05.2017 | Earth Sciences

New photocatalyst speeds up the conversion of carbon dioxide into chemical resources

29.05.2017 | Life Sciences

NASA's SDO sees partial eclipse in space

29.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>