Mount Sinai researchers develop mouse model to help find how a gene mutation leads to autism

December 16, 2010

Researchers from Mount Sinai School of Medicine have found that when one copy of the SHANK3 gene in mice is missing, nerve cells do not effectively communicate and do not show cellular properties associated with normal learning. This discovery may explain how mutations affecting SHANK3 may lead to autism spectrum disorders (ASDs). The research is currently published in Molecular Autism.

"We know that SHANK3 mutation plays a central, causative role in some forms of autism spectrum disorders, but wanted to learn more about how it does this," said Joseph Buxbaum, PhD, Director of the Seaver Autism Center and Professor of Psychiatry, Neuroscience and Genetics and Genomic Sciences at Mount Sinai School of Medicine. "These data provide critical insight into the mechanism behind the development of the cognitive and social changes associated with autism."

Previous research has shown that gene mutation in SHANK3 is associated with delayed language abilities, learning disability, and ASDs. A team of researchers at the Seaver Autism Center for Research and Treatment at Mount Sinai School of Medicine and the Intramural Research Program of the National Institute of Mental Health wanted to better understand the connection between the SHANK3 mutation and subsequent brain and behavioral difficulties. They examined mice genetically engineered to lack one copy of SHANK3, similar to patients who have a mutation in one copy of SHANK3, and compared the nerve cell activity of these mice with that of mice in a control group that did not have the mutation. They also examined social behaviors in these mice.

Mount Sinai scientists looked at brain activity in vitro and worked with the NIMH Laboratory of Behavioral Neuroscience, led by Jacqueline Crawley, PhD, to evaluate behavioral differences in the two groups of mice. The research team observed impaired communication between nerve cells in the mice with the SHANK3 mutation. They also found altered functional and structural plasticity in nerve cells, which is a cellular measure of the flexibility that occurs during learning, and in the synapses--the points of contact between nerve cells. Behavioral observations indicated reduced male-female social interactions in the SHANK3 mutant mice. The studies identify clear brain targets that can implicate drugs that can be therapeutic.

"These results have helped us determine a pathological mechanism behind neurodevelopmental disorders like autism," said Dr. Buxbaum. "Currently, the only therapeutic options for people with ASDs are to treat the symptoms of the disease, like anxiety or aggression. Armed with this breakthrough, we can begin testing drug compounds that treat the disease at its root cause, improving nerve cell communication. We hope and expect that, like other developmental disorders such as Fragile X syndrome, the use of mouse models will lead directly to clinical trials that can benefit patients."
-end-
The study was supported by a grant from the Seaver Foundation and a special multi-site grant awarded to co-authors Drs. Buxbaum, Crawley, Hof and Zhou from the Simons Foundation.

Autism and the ASDs are complex neurobiological disorders that inhibit a person's ability to engage in reciprocal social interactions and to develop social relationships, and are often accompanied by behavioral challenges. ASDs are diagnosed in one in 110 children in the United States, affecting four times as many boys as girls. The Centers for Disease Control and Prevention has called the high prevalence of ASDs a national public health crisis. A specific genetic disorder is identified in at least 15 to 25 percent of people with an ASD, and the proportion with an etiological diagnosis will continue to increase with the more widespread use of genetic testing.

The Seaver Autism Center provides comprehensive assessment and care for people with autism spectrum conditions. It includes a multi-disciplinary team of experts that use genetics, molecular biology, model systems, neuroimaging, and therapeutics to improve patient care and to develop the next generation of treatments. The Seaver Autism Center provides opportunities to participate in research studies aimed at understanding the causes of autism spectrum conditions and developing treatments. For more information, visit www.SeaverAutismCenter.org.

The article is available on the journal website.

About The Mount Sinai Medical Center

The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of few medical schools embedded in a hospital in the United States. It has more than 3,400 faculty in 32 departments and 15 institutes, and ranks among the top 20 medical schools both in National Institute of Health funding and by U.S. News & World Report. The school received the 2009 Spencer Foreman Award for Outstanding Community Service from the Association of American Medical Colleges.

The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. U.S. News & World Report consistently ranks The Mount Sinai Hospital among the nation's best hospitals based on reputation, patient safety, and other patient-care factors. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 530,000 outpatient visits took place.

For more information, visit www.mountsinai.org. Follow us on Twitter @mountsinainyc.

The Mount Sinai Hospital / Mount Sinai School of Medicine

Related Autism Articles from Brightsurf:

Autism-cholesterol link
Study identifies genetic link between cholesterol alterations and autism.

National Autism Indicators Report: the connection between autism and financial hardship
A.J. Drexel Autism Institute released the 2020 National Autism Indicators Report highlighting the financial challenges facing households of children with autism spectrum disorder (ASD), including higher levels of poverty, material hardship and medical expenses.

Autism risk estimated at 3 to 5% for children whose parents have a sibling with autism
Roughly 3 to 5% of children with an aunt or uncle with autism spectrum disorder (ASD) can also be expected to have ASD, compared to about 1.5% of children in the general population, according to a study funded by the National Institutes of Health.

Adulthood with autism
The independence that comes with growing up can be scary for any teenager, but for young adults with autism spectrum disorder and their caregivers, the transition from adolescence to adulthood can seem particularly daunting.

Brain protein mutation from child with autism causes autism-like behavioral change in mice
A de novo gene mutation that encodes a brain protein in a child with autism has been placed into the brains of mice.

Autism and theory of mind
Theory of mind, or the ability to represent other people's minds as distinct from one's own, can be difficult for people with autism.

Potential biomarker for autism
A study of young children with autism spectrum disorder published in JNeurosci reveals altered brain waves compared to typically developing children during a motor control task.

Autism often associated with multiple new mutations
Most autism cases are in families with no previous history of the disorder.

State laws requiring autism coverage by private insurers led to increases in autism care
A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health has found that the enactment of state laws mandating coverage of autism spectrum disorder (ASD) was followed by sizable increases in insurer-covered ASD care and associated spending.

Autism's gender patterns
Having one child with autism is a well-known risk factor for having another one with the same disorder, but whether and how a sibling's gender influences this risk has remained largely unknown.

Read More: Autism News and Autism Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.