GSE202046
Effect of  depletion of the Gne gene in Sol8 murine muscle cells
GNE myopathy is an adult onset neuromuscular disorder characterized by slowly progressive distal and proximal muscle weakness, caused by missense recessive mutations in the GNE gene. Although the  encoded bifunctional enzyme is well known as the limiting factor in the biosynthesis of sialic acid, no clear mechanisms have been recognized to account for the muscle atrophic pathology, and novel functions for GNE have been hypothesized.  No reliable animal model is available for the disease and cellular models from GNE myopathy patients' muscle cells (expressing the mutated protein) are less informative than expected.  In order to broaden our knowledge on GNE functions in muscle, we have generated a Gne knock out murine muscle cell lineage to identify the events resulting from the total lack of the protein. A thorough multi-omics analysis of both systems including transcriptomics, proteomics, phosphoproteomics and ubiquitination,  unraveled novel pathways for Gne, in particular its involvement  in cell cycle control and in the DNA damage/repair pathway.The elucidation of fundamental mechanisms of Gne in normal muscle may contribute to the identification of the disrupted functions in GNE myopathy, thus, to the definition of novel  biomarkers and possible therapeutic targets for this disease. Overall design: Comparative gene expression profiling analysis of RNA-seq data for Sol8 Gne KO and  WT cells