Thesis
Transcriptomic Profiling of Germline Versus Acute Sorbs2 Deletion in the Hippocampus
University of Iowa
Bachelor of Science (BS), University of Iowa
Spring 2026
Abstract
Sorbs2 is classically recognized as a cytoskeletal adaptor protein, yet its specific function within the central nervous system remains poorly understood. Genetic variants and declining expression levels of Sorbs2 have been linked to Alzheimer’s Disease (AD), highlighting a critical need to uncover its physiological role in neurons. In the brain, this role is distinguished by an enriched and uncharacterized neuron-specific exon (NSE). This NSE contains a canonical C2H2 zinc-finger domain (ZnF), suggesting dual-roles for Sorbs2 as a structural scaffold and direct nucleic acid regulator. In this study, we first map the expression profile of the Sorbs2 NSE in the adult hippocampus. Initial biochemical assays in Sorbs2 global knockout (gKO) mice revealed a counterintuitively mild change in the transcriptomic landscape, suggesting that early developmental neuroplasticity may compensate for the loss of Sorbs2. To bypass this compensatory remodeling, we utilized an AAV-Cre viral vector system to generate an acute, neuron-specific knockout (nKO) in the adult brain. Through a comparative transcriptomic analysis, we demonstrate that while germline deletion yields blunted molecular consequences, acute viral ablation of Sorbs2 causes post-transcriptional dysregulation. Transcript isoform usage and rMATS analyses identified profound alternative splicing cascades unique to the viral mediated model, unveiling new regulatory candidates for Sorbs2. Together, these findings position Sorbs2 as a contributor to neuronal gene expression and alternative splicing beyond its classical cytoskeletal role, and suggest potential implications for neuronal vulnerability in AD.
Details
- Title: Subtitle
- Transcriptomic Profiling of Germline Versus Acute Sorbs2 Deletion in the Hippocampus
- Creators
- Kaleb Feia - University of Iowa
- Contributors
- Lori Wallrath (Mentor) - University of IowaJared McLendon (Advisor) - University of Iowa
- Resource Type
- Thesis
- Project Type
- Honors Thesis
- Degree Awarded
- Bachelor of Science (BS), University of Iowa
- Degree in
- Biochemistry and Molecular Biology
- Date degree season
- Spring 2026
- Publisher
- University of Iowa
- Number of pages
- 37 pages
- Copyright
- Copyright © 2016 Caleb Feia
- Language
- English
- Academic Unit
- CLAS Honors Theses
- Record Identifier
- 9985176751802771
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