Multiple Defects in Muscle Regeneration in the HSALR Mouse Model of RNA Toxicity

Myotonic dystrophy type 1 (DM1) results from the toxicity of RNA produced from the mutant allele of the DMPK gene. The mechanism by which the toxic RNA causes muscular dystrophy in DM1 is unknown. Dystrophy in DM1 is associated with defective muscle regeneration and repair. Here, we used the BaCl₂-induced damage model of muscle injury to study muscle regeneration in the HSALR mouse model of DM1. We have previously shown delayed muscle regeneration and deleterious effects on satellite cell numbers in another mouse model of RNA toxicity using similar experimental approaches. We found that HSALR mice show no apparent deleterious effects on satellite cell number or early markers of muscle regeneration. Further analysis at later time points after damage showed increased numbers of internal nuclei as compared to control mice undergoing the same protocol. Muscle fiber type analysis using immunostaining for type IIA and IIB fibers identified a switch to slower fibers (increased fraction of IIA and reduced fraction of IIB fibers) after regeneration in HSALR mice as compared to regenerated muscle from wildtype mice.