%0 Preprint %T Zebrafish and cellular models of SELENON-Related Myopathy exhibit novel embryonic and metabolic phenotypes. %A Barraza-Flores P %A Moghadaszadeh B %A Lee W %A Isaac B %A Sun L %A Troiano EC %A Rockowitz S %A Sliz P %A Beggs AH %J bioRxiv %V 0 %N 0 %D 2024 Feb 26 %M 38464009 暂无%R 10.1101/2024.02.26.581979 %X SELENON-Related Myopathy (SELENON-RM) is a rare congenital myopathy caused by mutations of the SELENON gene characterized by axial muscle weakness and progressive respiratory insufficiency. Muscle histopathology commonly includes multiminicores or a dystrophic pattern but is often non-specific. The SELENON gene encodes selenoprotein N (SelN), a selenocysteine-containing redox enzyme located in the endo/sarcoplasmic reticulum membrane where it colocalizes with mitochondria-associated membranes. However, the molecular mechanism(s) by which SelN deficiency causes SELENON-RM are undetermined. A hurdle is the lack of cellular and animal models that show assayable phenotypes. Here we report deep-phenotyping of SelN-deficient zebrafish and muscle cells. SelN-deficient zebrafish exhibit changes in embryonic muscle function and swimming activity in larvae. Analysis of single cell RNAseq data in a zebrafish embryo-atlas revealed coexpression between selenon and genes involved in glutathione redox pathway. SelN-deficient zebrafish and mouse myoblasts exhibit changes in glutathione and redox homeostasis, suggesting a direct relationship with SelN function. We report changes in metabolic function abnormalities in SelN-null myotubes when compared to WT. These results suggest that SelN has functional roles during zebrafish early development and myoblast metabolism.