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

Abstract

Recurrent exertional rhabdomyolysis (RER) is frequently observed in race horses like trotters. Some predisposing genetic factors have been described in epidemiological studies. However, the exact aetiology is still unknown. A calcium homeostasis disruption was suspected in previous experimental studies, and we suggested that a transcriptome analysis of RER muscles would be a possible way to investigate the pathway disorder. The purpose of this study was to compare the gene expression profile of RER vs. control muscles in the French Trotter to determine any metabolic or structural disruption. 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 'tying-up' with high plasmatic muscular enzyme activities. Gene expression analysis was performed on the muscle biopsies using a 25K oligonucleotide microarray, which consisted of 24,009 mouse and 384 horse probes. Transcriptome analysis revealed 191 genes significantly modulated in RER vs. control muscles (P < 0.05). Many genes involved in fatty acid oxidation (CD36/FAT, SLC25A17), the Krebs cycle (SLC25A11, SLC25A12, MDH2) and the mitochondrial respiratory chain were severely down-regulated (tRNA, MT-ND5, MT-ND6, MT-COX1). According to the down-regulation of RYR1, SLC8A1 and UCP2 and up-regulation of APP and HSPA5, the muscle fibre calcium homeostasis seemed to be greatly affected by an increased cytosolic calcium and a depletion of the sarcoplasmic reticulum calcium. Gene expression analysis suggested an alteration of ATP synthesis, with severe mitochondrial dysfunction that could explain the disruption of cytosolic calcium homeostasis and inhibition of muscular relaxation.

Integrating genome and transcriptome profiling for elucidating the mechanism of muscle growth and lipid deposition in Pekin ducks

“…Accumulation of ALDOA during muscle growth was a coordinated process occurring progressively in either intrauterine life or in vitro myogenesis 46, 47 . Similar effects of ALDOA have been reported in several other animals (human, rat, pig, sheep, and horse) 48–52 . In the present study, the mRNA expression level of ALDOA increased by nearly five-fold from 3 to 6 weeks of age in CD, whereas no obvious change was observed in BD.…”

Physiological and pathological roles of mitochondrial SLC25 carriers

“…With regard to pathology, down-regulation of OGC has been reported in horse muscle with recurrent exertional rhabdomyolysis [141]. OGC may also modulate apoptosis.…”

“…In pathological states, SLC25a17 down-regulation (along with many other mitochondrial transcripts) was detected in horses presenting recurrent exertional rhabdomyolysis, a myopathy involving inhibition of muscular relaxation [141]. In that study, the authors proposed that the mitochondrial dysfunction derived from an excess of cytoplasmic calcium triggering ATP depletion could underlie the clinical signs of the disease.…”

From experimental design to functional gene networks: DNA microarray contribution to skin ageing research

“…It is therefore important to determine among the modulated genes those whose expression can be regulated by the same transcriptional factors or as products are involved within a given signalling pathway. Several free or commercial software integrating a combination of interactive and visualization tools have been developed to identify the involvement of the gene products in molecular interactions, pathways, diseases and processes (reviewed in refs [13] and [14], [15][16][17][18]). They are mainly based on text mining performed either on curetted publications or on an exhaustive list of published abstracts issued from PubMed, a bibliographic database for the biomedical literature provided by NCBI, the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/pubmed).…”