DEVELOPMENTALLY REGULATED ALTERNATIVE SPLICING IS PERTURBED IN TYPE 1 DIABETIC SKELETAL MUSCLE

Introduction: Type 1 diabetic patients can develop skeletal muscle weakness and atrophy by molecular mechanisms that are not well understood. Alternative splicing (AS) is critical for gene expression in the skeletal muscle, and its dysregulation is implicated in muscle weakness and atrophy. Therefore, we investigated whether AS patterns are affected in type 1 diabetic skeletal muscle contributing to skeletal muscle defects. Methods: AS patterns were determined by reverse transcription- polymerase chain reaction and levels of RNA binding proteins were assessed by Western blot in type 1 diabetic mouse skeletal muscle and during normal mouse skeletal muscle development. Results: Five genes with critical functions in the skeletal muscle are misspliced in type 1 diabetic skeletal muscle, resembling their AS patterns at embryonic stages. AS of these genes undergoes dramatic transitions during skeletal muscle development, correlating with changes in specific RNA binding proteins. Conclusion: Embryonic spliced variants are inappropriately expressed in type 1 diabetic skeletal muscle.