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

The study explores the potential cause of recurrent exertional rhabdomyolysis (RER) in French Trotter horses by examining the alterations in genetic expression in the muscle tissue. The findings suggest that RER may be linked to disruptions in energy production and cytosolic calcium regulation in horse muscles.

Understanding Recurrent Exertional Rhabdomyolysis (RER)

• RER is a common disease in some racing horses such as French Trotters and it’s characterized by severe muscle damage and cramping in response to intense exercise or stress.
• While some predisposing genetic factors are noted in these types of horses, the exact cause of RER remains uncertain.
• Prior studies have suggested that RER may be associated with a disruption in calcium homeostasis or balance in the body.

Study Methodology

• The study carried out a transcriptome analysis on muscle biopsies from 15 French Trotter horses. Of these, 10 were healthy control horses, and 5 were RER horses suffering from ‘tying-up’, a muscular disorder defined by high plasma muscle enzyme activities.
• The researchers examined the gene expression profile in both types of horses using a 25K oligonucleotide microarray composed of 24,009 mouse probes and 384 horse probes.

Study Findings

• The research identified 191 genes that showed significant changes in the RER horses compared to the control horses.
• Many genes associated with energy production, such as those involved in fatty acid oxidation, the Krebs cycle, and the mitochondrial respiratory chain, appeared to be drastically down-regulated.
• Furthermore, it seemed that muscle fiber calcium homeostasis was severely affected, indicated by decreased regulation of RYR1, SLC8A1, and UCP2, and increased regulation of APP and HSPA5. This points to a potential increase in cytosolic calcium and depletion of calcium in the sarcoplasmic reticulum.

Implications of the Study

• The gene expression analysis suggested a potential disruption of ATP synthesis and severe mitochondrial dysfunction which could contribute to cytosolic calcium homeostasis disruption and prevent muscle relaxation.
• This investigation provides insight that may help pin-point the exact cause of RER and can offer a pathway for further research and the development of potential treatment strategies.