Kara G. Margolis, MD New York University Angelman and the Gut
$250,000
GI problems occur in up to 80% of people with Angelman’s Syndrome (AS). The most commonly reported issues include constipation, gastroesophageal reflux, and abdominal pain. Further, GI problems are associated in neurodevelopmental conditions with both challenges in behavior and cognition. Yet, the etiology of GI problems in individuals with Angelman’s syndrome are completely unknown nor is it known whether improvement in GI symptoms would improve behavioral and/or cognitive outcomes.
It is known that the gene that is linked to AS, UBE3A, is found in the nerve cells in the brain. It is also, however, located throughout the gastrointestinal tract and may thus play a key role in the GI issues that affect people with AS. Further, it is shown that the gut can impact brain morphology and function. It is thus possible that modification of UBE3A in the gut may also help the more central issues (e.g., cognition, mood and neurobehavior) that these individuals face. Fortunately, mouse models with UBE3A mutations exist that express similar behavioral and brain phenotypes to those seen in AS.
This study will examine the gastrointestinal tract of these mice to determine precisely where UBE3A is located in the intestine and whether these mice manifest similar GI problems as those seen in the AS population. These studies will provide us with the capability to then analyze the gut epithelium and enteric nervous system to explore locations and contributions of UBE3A to both systems in the gut and also their impacts on the brain and neurobehavior.
Project Update
See a Q & A session with Dr. Margolis. She answered questions about how she became interested in this research, how the presence of the UBE3A gene in the gut might be related to GI problems, the hypothesis for her research and potential therapeutic implications.