Understanding the Disease Pathogenesis of X-linked Myotubular Myopathy

X-linked myotubular myopathy (XLMTM) is a fatal condition caused by mutations in myotubularin 1 (MTM1), which encodes a lipid phosphatase. Despite our increased understanding of XLMTM pathology, how MTM1 functions in skeletal muscle is unknown. To address this, I performed a phenotypic and molecular analysis of Mtm1 knockout mice throughout disease development. These mice exhibit histopathological abnormalities such as central nuclei, muscle hypotrophy, and increased oxidative staining. Alterations in transcriptome (gene expression), epigenome (DNA methylation) and proteome (protein levels of disease markers) are also characteristics of this model. As a secondary aim, I performed AP-MS experiments using a MTM1-6xHis mouse to identify the MTM1 interactome in the context of skeletal muscle. Lastly, as a third aim, I characterized Mtm1 KO C2C12 cell line as a model for XLMTM. This work herein explores the function and interactome of MTM1 in skeletal muscle and expands our current understanding of XLMTM.M.Sc.2021-11-30 00:00:0