Featured Research

from universities, journals, and other organizations

Engineering Autism: Mice With Extra Chromosome Region Show Many Autistic Signs

Date:
June 26, 2009
Source:
Cell Press
Summary:
Mice who inherit a particular chromosomal duplication from their fathers show many behaviors associated with human autism, researchers report. The duplicated chromosomal region in mice is the equivalent of human chromosome 15q11-13, the most frequent cytogenetic abnormality observed in autism, accounting for some five percent of all cases.

Mice who inherit a particular chromosomal duplication from their fathers show many behaviors associated with human autism, researchers report in the June 26th issue of the journal Cell. The duplicated chromosomal region in mice is the equivalent of human chromosome 15q11-13, the most frequent cytogenetic abnormality observed in autism, accounting for some five percent of all cases.

Related Articles


The engineered mice validate the human chromosome abnormality as one cause of the disease, the researchers said. They will also serve as an invaluable tool for therapeutic development.

"We know several mice as 'putative' models of autism, which show face validity that they are similar to human patients," said Toru Takumi of Hiroshima University in Japan. "In addition to these similar phenotypes, our mice have construct validity," meaning that their symptoms are traced to the same biological cause.

Autism is a common and heterogeneous neuropsychiatric disorder with manifestations of impaired social interaction and communication as well as repetitive behavior or restricted interest, the researchers explained. It is also one of the most heritable of all mental disorders, suggesting that genetic factors play an important role in development of the disease.

Scientists have studied many gene candidates, and mice carrying some of those mutations do show some signs. Still the molecular pathways underlying autism remain largely mysterious.

Chromosomal abnormalities are thought to account for 10 to 20 percent of cases and duplication of chromosome 15q11-13 is the only recurrent aberration so far linked to the disease.

In the new study, Takumi's team generated mice with a duplication of a region on their chromosome 7, mirroring the autism-linked abnormality seen in humans. Mice who inherit that abnormality from their fathers show poor social interaction, behavioral inflexibility, abnormal ultrasonic vocalizations and indications of anxiety, the results of extensive behavioral testing now show.

For instance, when given the option of spending time alone or in the presence of a stranger mouse, normal mice will often choose to hang out with the stranger, Takumi said. Mice with the chromosomal abnormality, on the other hand, more often choose to spend time with inanimate objects over fellow mice.

In tests of spatial memory, in which mice are trained to swim to a hidden platform, animals with the paternally inherited duplication were less able to adapt to changes in the platform's location than normal mice were. Another test, in which mice have to locate the correct hole to exit a box, showed similar results.

"We were honestly surprised to see behavioral inflexibility in two different reversal tests of learning and two different backgrounds," Takumi said. "Higher ultrasonic calls from pups with paternal duplication were unexpected" too. It's also hard to say exactly what those unusual calls mean for the mice, given scientists' limited understanding of mouse communication.

In other tests, the mice showed more signs of fear or anxiety, a feature common in autistic individuals.

The researchers also found molecular-level evidence that the duplication can lead to changes in a receptor for serotonin, a nerve messenger that acts as a growth factor in the immature brain. Those changes stem from different levels of one brain-specific small nucleolar RNA (snoRNA), known as MBII52, a molecule that is known to be involved in physiologically important "edits" to the receptor.

Because the gene that encodes MBII52 is "maternally imprinted," its expression in mice with the inherited duplication from their father was double that of normal mice or those who inherited the same abnormality from their mothers, they report. (Imprinted genes are chemically modified to prevent their expression.) Studies in cultured neurons showed that those changes to MBII52 are associated with an altered neural response, suggesting that changes in serotonin signals might underlie the aberrant behaviors exhibited by the animals.

In addition to those insights, the mice may yet hold many more clues for understanding autism and potential for new treatments.

"The link between social behaviors in rodents and social behavior in humans is difficult to establish," the researchers concluded. "Our model mouse will be valuable not only for therapeutic studies but also provides a starting point for more detailed genetic analysis directed toward understanding the etiology of developmental brain disorders."


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "Engineering Autism: Mice With Extra Chromosome Region Show Many Autistic Signs." ScienceDaily. ScienceDaily, 26 June 2009. <www.sciencedaily.com/releases/2009/06/090625133053.htm>.
Cell Press. (2009, June 26). Engineering Autism: Mice With Extra Chromosome Region Show Many Autistic Signs. ScienceDaily. Retrieved November 26, 2014 from www.sciencedaily.com/releases/2009/06/090625133053.htm
Cell Press. "Engineering Autism: Mice With Extra Chromosome Region Show Many Autistic Signs." ScienceDaily. www.sciencedaily.com/releases/2009/06/090625133053.htm (accessed November 26, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Wednesday, November 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) A new study links greater authority with increased depressive symptoms among women in the workplace. Video provided by Newsy
Powered by NewsLook.com
Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. 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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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