bioRxiv preprint doi: https://doi.org/10.1101/2021.08.24.457331; this version posted August 26, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Loss of full-length dystrophin expression results in major cell- autonomous abnormalities in proliferating myoblasts. Maxime R. F. Gosselin1, Virginie Mournetas2, Malgorzata Borczyk3, Lukasz Bozycki1,4, Michal Korostynski3, Samuel Robson1,5, Christian Pinset6, Dariusz C. Górecki1 * 1School of Pharmacy and Biomedical Sciences, University of Portsmouth, PO1 2DT, Portsmouth, UK 2INSERM UEVE UMR861, I-STEM, AFM, 28 rue Henri Desbruères, 91100 Corbeil-Essonnes, France 3Laboratory of Pharmacogenomics, Maj Institute of Pharmacology PAS, Krakow, Poland 4Laboratory of Biochemistry of Lipids, Nencki Institute of Experimental Biology, Warsaw, Poland. 5Centre for Enzyme Innovation, University of Portsmouth, PO1 2DT, Portsmouth, UK 6CNRS, I-STEM, AFM, 28 rue Henri Desbruères, 91100 Corbeil-Essonnes, France *Corresponding author (
[email protected]) Keywords DMD, dystrophin, mdx, myoblast, transcriptomics Abstract Background. Duchenne muscular dystrophy (DMD) is the most common inherited muscle disease that leads to severe disability and death in young men. DMD is caused by out-of-frame mutations in the largest known gene, which encodes dystrophin. The loss of DMD gene expression manifests in progressive degeneration and wasting of striated muscles aggravated by sterile inflammation. Current conventional treatments are palliative only, whereas experimental therapeutic approaches focus on the re-expression of dystrophin in myofibers. However, recent studies established that DMD pathology begins already in prenatal development prior to myofiber formation while, in adult muscle, it affects satellite (stem) cells and the proper development of myofibers.