Mount Sinai Researchers Generate First In-Depth Characterization of a Genetically Modified Rat Model for Autism and Intellectual Disability
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
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across eight hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2024-2025.
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