Browsing by Author "Abbas, Salma Magdy Hussein Jr"

Elevated low-density lipoprotein cholesterol (LDL-C), hypercholesterolemia, is characterized by complex and poorly understood genetic contributions. Cellular LDL uptake mediated by the LDL receptor is pivotal to disease progression. After LDL internalization LDLR is recycled to the plasma membrane. Genetic mutations are known to exist in factors driving LDLR recycling but their contribution to hypercholesterolemia is not known. SNX17 has been postulated to be important for LDLR recycling. The goal of this study was to investigate the effect of SNX17 on cellular LDL uptake and to evaluate whether functional characterization of SNX17 gene variants can be performed. At the same time, adjusting an existing semi-automated analysis pipeline to generate expression constructs for SNX17 genetic variants. In this study, using an SNX17 knock-out cell line and an SNX17 rescue cell line (SNX17 knock-out cells transfected with GFP-SNX17 construct), it was shown that SNX17 might have a role in LDL uptake. The semi-automated workflow for generating genetic variants was successfully adopted to SNX17, warranting further experiments to define the optimal conditions for the functional characterization of SNX17 gene variants. This thesis sets the foundation for a deeper understanding of SNX17 in LDLR recycling and provides first insights into the potential regulation of this pathway, while also initiating the way for the later characterization of SNX17 variants. Hence, functional genomic studies together with the functional characterization of genetic variants in LDLR recycling factors can improve our understanding of how genetic variation contributes to disease progression and develop better risk assessment tools.