Transcriptome analysis of muscle in horses suffering from recurrent exertional rhabdomyolysis revealed energetic pathway alterations and disruption in the cytoplasmic calcium regulation

The purpose of this study was to compare the gene expression profile of recurent exercise rhabdomyolysis vs control muscles in French Trotter to determine any metabolic or structural disorder. Transcriptome analysis revealed 191 genes significantly modulated in rhabdomyolysis vs control muscles (p<0.05). Many genes involved in the fatty acid oxidation, the TCA cycle and the mitochondrial respiratory chain were severely down-regulated. The muscle fibers were under hypoxia and oxidative stress conditions which stimulated glycolysis. The muscle fiber calcium homeostasis was greatly affected towards an increase of cytoplasmic calcium and a depletion of the sarcoplasmic reticulum calcium. Gene expression analysis revealed an alteration of the aerobic ATP synthesis with a severe mitochondrial dysfunction which could explain the disruption of the cytoplasmic calcium regulation and a muscular relaxation disorder. Total RNA was extracted from the gluteal medius and longissimus lumborum muscles after biopsies in 15 French Trotter horses including 10 controls and 5 RER horses affected by rhabdomyolysis with high plasmatic muscular enzyme activities. Gene expression analysis was performed on the muscle biopsies using a 25K oligonucleotide microarray.