• Press Release

Mount Sinai Researchers Generate First In-Depth Characterization of a Genetically Modified Rat Model for Autism and Intellectual Disability

  • (January 30, 2017)

Researchers at The Seaver Autism Center for Research and Treatment at Mount Sinai have generated and characterized a genetically modified rat model of autism and intellectual disability, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published January 31 in the journal eLife. Researchers report that in this novel rat model, the hormone oxytocin significantly improved social memory, attention, and nerve cell activity.

The Mount Sinai study focused specifically on the production and characterization of a first genetically modified rat model for Phelan-McDermid syndrome, a developmental disorder with high rates of autism, intellectual disability, attention deficits, and severe language delay. One or more of these symptoms is found in up to 10 percent of children, with limited medicines available for treatment.  Phelan-McDermid syndrome is caused by a mutation in a gene called Shank3, leading to a malfunction of nerve cells, especially at the region known as the synapse, where nerve cells communicate with each other.

“Our rat model provides the research community with a valuable tool to study how altered function of synapses and nerve cells leads to subsequent deficits in behavior and cognition that are associated with multiple developmental disorders, including Phelan-McDermid syndrome.” says Hala Harony-Nicolas, PhD, an instructor at The Seaver Autism Center, and the lead scientist on this study. “Such studies require sophisticated approaches that are significantly more challenging in other model systems as compared to rats, underscoring the value of this model.”

The new model, referred to as the Shank3-deficient rat, mimics a human Shank3 mutation and exhibits deficits in a form of social behavior that depends on long-term memory, attention, and communication between nerve cells. The research team discovered that behavioral and synaptic deficits could be improved by treatment with the pro-social hormone oxytocin, which is known to be a powerful modulator of mammalian social behavior. Oxytocin was also able to reverse attention deficits that were not related to any social context, a finding that has not been seen in previous studies.   

These findings provide important leads into how Shank3 plays a role in synapse development and function and, ultimately, behavior. In addition, the effect of oxytocin on reversing developmental deficits provides a tool to understand the causes of nerve cell and behavioral deficits and to develop novel treatments.

“One of the most surprising and promising findings of this study is the effect oxytocin had on attention deficits beyond its known effects on social memory,” says Joseph D. Buxbaum, PhD, senior author of the publication and Director of The Seaver Autism Center. “This study is important for understanding developmental disorders broadly and is also the first to indicate that individuals with Phelan-McDermid syndrome may particularly benefit from oxytocin treatment, a hypothesis that is being further examined in ongoing clinical studies at the Seaver Autism Center.”

The study was funded by the Beatrice and Samuel A. Seaver Foundation, the National Institute of Mental Health, the Human Frontier Science Program, the Israel Science Foundation, Autism Speaks, and by a generous gift from William G. Gibson and Paulina Rychenkova, PhD.

About the Seaver Autism Center for Research and Treatment at Mount Sinai
The Seaver Autism Center for Research and Treatment at Mount Sinai conducts progressive research studies aimed at understanding the multiple causes of autism spectrum disorder (ASD).  The multidisciplinary team is composed of experts in the fields of genetics, molecular biology, model systems, neuroimaging, biomarkers, diagnosis, and experimental therapeutics who are dedicated to discovering the biological causes of ASD.  The Center strives to develop innovative diagnostics and treatments for integration into the provision of personalized, comprehensive assessment and care for people with ASD.  The Seaver Autism Center was founded through the generous support of the Beatrice and Samuel A. Seaver Foundation. For more information, visit www.seaverautismcenter.org.


About the Mount Sinai Health System

The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Geriatrics, Gynecology, Nephrology, Neurology/Neurosurgery, and Orthopedics in the 2019-2020 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 12th nationally for Ophthalmology and Mount Sinai South Nassau is ranked 35th nationally for Urology. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and Mount Sinai South Nassau are ranked regionally.

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