Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Biochemistry

Supervisor(s)

Dr. Nathalie Berube

Abstract

ATRX is a Rad54 translocase homolog implicated in regulating the epigenetic environment of heterochromatin, mitosis, and gene transcription. Myelin is a specialized membrane encompassing axons of neurons, allowing for efficient propagation of action potentials. CNS myelin arises via oligodendrocyte precursor cell (OPC) differentiation into myelinating oligodendrocytes (OLs), which then extend and wrap axons. Myelination is a tightly regulated process, however the mechanisms involved have yet to fully manifest. Here, we report that ATRX loss results in hypomyelination due to a defect in OPC differentiation and OL maturation, as ATRX loss did not affect OPC production, proliferation, or cholesterol biosynthesis. Additionally, myelin sheath formation was unaffected when ATRX was lost specifically from OLs, suggesting a non cell-autonomous role of ATRX in myelination. Clarifying the role of ATRX in myelination presents a novel mechanism that regulates myelin sheath formation, and findings from this study will benefit future treatments of myelin disorders, including ATR-X.

Available for download on Saturday, September 01, 2018


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