Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults, characterised by myotonia, muscle weakness and progressive muscle atrophy. DM1 is caused by the expression of mutated RNAs containing expansions of CUG repeats (CUGexp-RNA) that form nuclear aggregates and alter the activity of RNA-binding proteins and the metabolism of certain RNAs. Although a number of muscular symptoms such as myotonia have been associated with abnormalities in the regulation of alternative splicing of target transcripts, the mechanisms involved in the dystrophic process are still poorly understood and animal models of DM1 do not reproduce, or only partially reproduce, this most disabling phenotype of the disease. Using new mouse models enabling cell/tissue-specific expression of the DM1 mutation in adults, we will study muscle changes following specific expression of CUGexp-RNA in muscle fibres and/or in muscle stem cells in order to determine their respective contribution to the dystrophic process that progressively develops in DM1 patients. Physiological and histological analyses of the muscles will be supplemented by transcriptomic analyses using RNAseq and also at the level of single nuclei using snRNAseq in order to identify and characterize the molecular alterations induced by the expression of CUGexp-RNA that will affect their cellular fate. Spatial transcriptomic or RNAscope analyses will complement these analyses in order have a comprehension view of the cellular mechanisms involved in the degenerative process found in the skeletal muscle of DM1 patients.