Abstract
Myotonic dystrophy type 1 (DM1) is a severe autosomal dominant neuromuscular disease in which the musculoskeletal system contributes substantially to overall mortality and morbidity. DM1 stems from a noncoding CTG trinucleotide repeat expansion in the DMPK gene. The human skeletal actin long repeat (HSA(LR)) mouse model reproduces several aspects of the disease, but the muscle-wasting phenotype of this model has never been characterized in vivo. Herein, we used quantitative MRI to measure the fat and muscle volumes in the leg compartment (LC) of mice. These acquired data were processed to extract relevant parameters such as fat fraction and fat infiltration (fat LC/LC) in HSA(LR) and control (FBV) muscles. These results showed increased fat volume (fat LC) and fat infiltration within the muscle tissue of the leg compartment (muscle LC), in agreement with necropsies, in which fatty clumps were observed, and consistent with previous findings in DM1 patients. Model mice did not reproduce the characteristic impaired fat fraction, widespread fat replacement through the muscles, or reduced muscle volume reported in patients. Taken together, the observed abnormal replacement of skeletal muscle by fat in the HSA(LR) mice indicates that these mice partially reproduced the muscle phenotype observed in humans.