Date of Award
December 2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biomedical Engineering
First Advisor
Abraam Yakoub
Second Advisor
Bo Liang
Abstract
Mouse models are indispensable for life sciences research in order to understand gene functions and disease mechanisms. Lack of appropriate models has hampered the robust understanding of biological processes, animal physiology, and pathophysiology. For example, most of the existing approaches to mouse models, such as expressing (or knocking out) a gene of interest constitutively and throughout the whole animal body, have limited our ability to deconstruct human disease and behavior, in a tissue- and cell-type specific manner, and one cell type at a time. Fortuitously, biological engineering (bioengineering) approaches could be developed and harnessed to generate robust animal models of disease that allow dissecting the biological mechanisms in a tissue- and cell-type-specific manner, for disease understanding and research. In this dissertation, we developed mouse models expressing genes of interest in a tissue- and cell-type-specific manner, enabling precise determination of how particular cell and tissue types contribute to disease mechanisms, with a specific focus on the brain as the target of interest. First, we investigated a virus vector-based approach for targeted gene delivery to the mouse brain using stereotaxic injections and specialized instruments, in order to obtain brain-wide but cell-type-specific gene expression. We validated this approach using molecular and histological approaches. Second, we employed a cell-type-specific transgenic mouse model. We tested the ability of the transgenic model to recapitulate brain disease symptoms observed in patients and to decipher disease mechanisms, using COVID-19 as a proof-of-concept model, restricting the infection to a particular tissue, therefore enabling determine the role of these tissues in disease pathology. Through this work, we were able to advance the fields of bioengineering and life sciences in general, with new approaches to gene manipulation in vivo and mouse model development. This work has significant and broad impacts on understanding biological and physiological mechanisms and on understanding and treating human disease.
Recommended Citation
Ibrahim, Osama Ahmed Galal Mohamed, "Genetic Engineering Of Mouse Models To Understand Gene Functions And Disease Mechanisms" (2025). Theses and Dissertations. 8224.
https://commons.und.edu/theses/8224