Honors Theses

Behavioral Phenotyping of a Neuron-specific Inducible Cre-Conditional SERCA2 Knockout Mouse Model

Advisor

Pothitos M. Pitychoutis, Ph.D.

Department

Biology

Publication Date

4-22-2026

Document Type

Honors Thesis

Abstract

Due to the major role calcium (Ca2+) plays in neuronal functions, brain development, and programmed cell death, regulation of intracellular Ca2+ homeostasis is of great interest in the field of Neuroscience. One critical mechanism that maintains low cytosolic Ca2+ concentrations in neurons pertains to the pumping of Ca2+ ions into the endoplasmic reticulum (ER) for storage, a process regulated by the sarco-endoplasmic reticulum Ca2+ ATPase 2 (SERCA2). Dysregulation of SERCA2, as well as other Ca2+ regulatory proteins, has been implicated in the pathophysiology of neurodevelopmental and neurodegenerative diseases. Evidence from our research group and others suggests that developmental deletion of the Serca2 gene either ubiquitously throughout the mouse brain or within specific neuronal sub-populations is embryonically lethal. In the context of this honors thesis research, we generated a novel transgenic tamoxifen-inducible Cre-loxP conditional knockout mouse model in which Serca2 deletion was targeted to the projection neurons of adult mice. Preliminary phenotypic behavioral characterization following neuron-specific Serca2 deletion was conducted in adult mice through a battery of behavioral tests focusing on assessing locomotor activity (i.e., open field test), as well as anxiety-like (i.e., dark/light box test and open field test) and compulsive-like (i.e., marble burying test) behaviors. In the context of this honors thesis, we provide preliminary evidence that furthers our understanding of the neuronal functions of SERCA2 in the brain and behavior.

Permission Statement

This item is protected by copyright law (Title 17, U.S. Code) and may only be used for noncommercial, educational, and scholarly purposes.

Keywords

Undergraduate research

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