Investigating AP3B2 Behavioral Phenotypes in a Mouse Model for Epileptic Encephalopathy

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Interdisciplinary Centers, Units and Projects::Center for Undergraduate Research and Fellowships (CURF)::Fall Research Expo
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Medicine and Health Sciences
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Epilepsy
Neurology
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2025-09-06
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Yastika Singh
Yifan Wei
Eric Marsh
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Abstract

Early onset epileptic encephalopathy (EOEE) is a heterogeneous class of neurological disorders characterized by frequent refractory seizures, or short bursts of abnormal neuronal activity, developmental delay or regression, and more. There are currently hundreds of genetic mutations associated with EOEEs, including AP3B2, a gene that in neurons, encodes for proteins that sort and transport vesicle membrane proteins between the soma and terminus. An autosomal recessive mutation of AP3B2 has been found to cause EOEEs by disrupting neurotransmitter release. In this study, the behavioral phenotype of mice with the AP3B2 mutation was studied through analysis of three behavioral tests: Open Field, Barnes Maze, and Rota Rod. The Open Field test measures anxiety by observing the travel patterns of mice in an open-topped box for fifteen minutes. The Barnes Maze test tests memory and learning in mice. The Rota Rod test also tests learning by observing if mice learn to not fall off a spinning wheel over repeated trials. Behavioral tests were conducted and recorded using the ANY-maze software and then analyzed using JASP, an open-source, free, statistical software. The Open Field results indicated that heterozygous mice had a significantly lower ratio of center/outside entries and center/outside time spent than wild type and mutant mice. The Rota Rod results indicated that wild type mice performed better than mutant and heterozygous mice, suggesting reduced motor coordination due to the AP3B2 mutation. These findings could help better understand the AP3B2 mutation’s behavioral outcomes, paving the way for genetic therapies in the future.

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2025-09-15
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Funding for this project was generously provided by the Penn Undergraduate Research Mentoring (PURM) program.
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