Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


New findings help pinpoint autism’s genetic roots


By deleting a gene in certain parts of the brain, researchers at UT Southwestern Medical Center have created mice that show deficits in social interaction that are reminiscent of humans with autism spectrum disorders.

The investigators also found physical abnormalities in the brains that mimic some cases of autism, showing that the research animals can be useful in studying the mysterious condition.

The finding — to be published in the May 4 issue of the journal Neuron — confirms recent indications that a mutation in this particular gene could cause at least some forms of autism, said Dr. Luis F. Parada, director of the Center for Developmental Biology and the study’s senior author. Dr. Parada also directs the Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration.

"The exciting thing about this mouse is it helps us to zero in on at least one anatomic location of abnormality, because we targeted the gene to very circumscribed regions of the brain," he said. "In diseases where virtually nothing is known, any inroad that gets into at least the right cell or the right biochemical pathway is very important."

Autism is a brain disorder in which people have trouble with communication and social interaction and engage in repetitive movements. Usually manifesting in childhood, it affects about one in every 250 people, primarily males.

The researchers focused on a gene called Pten, which is also known to suppress cancers in humans. Some people with autism have mutations in Pten, but it has been unclear if that’s what causes the disease, Dr. Parada said. To test that hypothesis, the researchers deleted the gene in the front of the mouse brain and in areas of the hippocampus, a structure involved in memory and other functions.

Mice, which are social animals, are a good model for studying the disease, Dr. Parada said. Their behavior can be studied when they are exposed to other mice, when they are provided with inanimate objects and material for making nests, and when they are placed in unfamiliar environments.

In each of those conditions, the mutant mice were distinctly different from normal mice that came from the same litter.

Mice lacking the Pten gene were generally uninterested in unfamiliar mice, while normal mice approached the strangers. When mutant mice were exposed to both an inanimate object and another mouse, they showed about equal interest in each — echoing the way children with autism prefer toys to people — while the normal mice preferred the other mouse.

When given raw material for nesting, the mutants ignored it, while the normal mice teamed up to build nests. And the pups of mutant females often died from lack of maternal care.

The genetically altered mice were also hypersensitive to stressful stimuli, such as being picked up, being subjected to a sudden noise, or being put in a lighted or open area. People with autism are similarly overly sensitive to sensory stimuli.

The mutant mice’s brains were also noticeably altered in the areas where the gene was deleted. The nerve cells were thicker than normal and had a higher-than-normal number of connections to other nerve cells. This may lead to the sensory overload that people with autism experience, Dr. Parada said.

"It would be really exciting if it turned out that we’ve zeroed in on the anatomical regions where things go wrong in autistic patients, regardless of how the autism occurs," he said, adding that the next step in the research is to treat the mice with drugs to see whether it’s possible to reverse the condition.

Autism-like syndromes are being studied at UT Southwestern from another angle through the work of Dr. Lisa Monteggia, assistant professor of psychiatry.

Her investigation of the role of a gene called MeCP2 in mediating autistic-like behavior has been published recently in the journals Biological Psychiatry and Current Biology. Mutations in MeCP2 occur in a pervasive developmental disorder called Rett syndrome, a human disease that shares many clinical features with autism. Mutations in MeCP2 also have been identified in autism patients.

In Biological Psychiatry, she described how the selective deletion of MeCP2 in the brains of mice — in similar areas as those targeted by Dr. Parada — creates many of the features of Rett syndrome that are also observed in autism patients, including reduced social interaction, abnormal repetitive behavior and increased anxiety.

Current Biology reported her collaborative study with Dr. Ege Kavalali, associate professor in the Center for Basic Neuroscience, in which recorded signals from nerve cells in the mouse brain showed that in those lacking MeCP2, there was an imbalance between signals that excite nerve cells and those that inhibit neural activity. Such an imbalance in nerve transmission has been hypothesized as a feature of human autistic disorders; however, this is the first report demonstrating such an imbalance.

Lead authors in the Pten study from the Center for Developmental Biology were Dr. Chang-Hyuk Kwon, postdoctoral researcher; former graduate student Bryan Luikart, now at Oregon Health & Science University; and Dr. Craig Powell, assistant professor of neurology and psychiatry at UT Southwestern.

The work was supported by the American and Lebanese Associated Charities, the National Institutes of Health and the American Cancer Society.

UT Southwestern scientists participating in the MeCP2 research were Erika Nelson, student research assistant in psychiatry, and Terry Gemelli, former research associate in psychiatry.

Dr. Monteggia’s research is supported in part by the National Alliance for Autism Research, Once Upon A Time …, and the Rett Syndrome Research Foundation.

Aline McKenzie | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Ice shelf vibrations cause unusual waves in Antarctic atmosphere

25.10.2016 | Earth Sciences

Fluorescent holography: Upending the world of biological imaging

25.10.2016 | Power and Electrical Engineering

Etching Microstructures with Lasers

25.10.2016 | Process Engineering

More VideoLinks >>>