DOI
https://doi.org/10.25772/8AA7-PX83
Defense Date
2023
Document Type
Thesis
Degree Name
Master of Science
Department
Biochemistry
First Advisor
Sandeep Singh
Second Advisor
Tomasz Kordula
Third Advisor
Jeffrey Dupree
Abstract
YKL-40, also known as CHI3L1, is a chitinase-like protein that is expressed by several cells in a variety of organisms. Several different functions have been assigned to YKL-40, such as promoting cell growth and proliferation, regulating the ECM, protect cells from apoptosis, and play a role in inflammation. While there is extensive research done on YKL-40, very little is known on its role in the CNS. This is despite YKL-40 being highly expressed during several neuroinflammatory conditions, such as Alzheimer’s disease and multiple sclerosis. We investigated the expression of YKL-40 in the developmental CNS of mice and determined that expression increases as mice brains develop. Expression levels are higher in the cerebellum and the hippocampus than in the cortex. YKL-40 expression primarily colocalizes with astrocytes. Interestingly, YKL-40 expression tended to be more highly expressed in the corpus callosum and white matter, areas with high myelin and oligodendrocyte density. Finally, two lines of YKL-40 cell specific tamoxifen-inducible knockout lines were developed, one for astrocytes and one for microglia. The astrocyte knockout line was developed first, and injection of tamoxifen has shown partial success in knocking out YKL-40 expression in astrocytes.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-9-2023