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BMC veterinary research2009; 5; 29; doi: 10.1186/1746-6148-5-29

Gene expression profiling in equine polysaccharide storage myopathy revealed inflammation, glycogenesis inhibition, hypoxia and mitochondrial dysfunctions.

Abstract: Several cases of myopathies have been observed in the horse Norman Cob breed. Muscle histology examinations revealed that some families suffer from a polysaccharide storage myopathy (PSSM). It is assumed that a gene expression signature related to PSSM should be observed at the transcriptional level because the glycogen storage disease could also be linked to other dysfunctions in gene regulation. Thus, the functional genomic approach could be conducted in order to provide new knowledge about the metabolic disorders related to PSSM. We propose exploring the PSSM muscle fiber metabolic disorders by measuring gene expression in relationship with the histological phenotype. Results: Genotypying analysis of GYS1 mutation revealed 2 homozygous (AA) and 5 heterozygous (GA) PSSM horses. In the PSSM muscles, histological data revealed PAS positive amylase resistant abnormal polysaccharides, inflammation, necrosis, and lipomatosis and active regeneration of fibers. Ultrastructural evaluation revealed a decrease of mitochondrial number and structural disorders. Extensive accumulation of an abnormal polysaccharide displaced and partially replaced mitochondria and myofibrils. The severity of the disease was higher in the two homozygous PSSM horses.Gene expression analysis revealed 129 genes significantly modulated (p < 0.05). The following genes were up-regulated over 2 fold: IL18, CTSS, LUM, CD44, FN1, GST01. The most down-regulated genes were the following: mitochondrial tRNA, SLC2A2, PRKCalpha, VEGFalpha. Data mining analysis showed that protein synthesis, apoptosis, cellular movement, growth and proliferation were the main cellular functions significantly associated with the modulated genes (p < 0.05). Several up-regulated genes, especially IL18, revealed a severe muscular inflammation in PSSM muscles. The up-regulation of glycogen synthase kinase-3 (GSK3beta) under its active form could be responsible for glycogen synthase (GYS1) inhibition and hypoxia-inducible factor (HIF1alpha) destabilization. Conclusions: The main disorders observed in PSSM muscles could be related to mitochondrial dysfunctions, glycogenesis inhibition and the chronic hypoxia of the PSSM muscles.
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Publication Date: 2009-08-07 PubMed ID: 19664222PubMed Central: PMC2741442DOI: 10.1186/1746-6148-5-29Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research explored the genetic expressions and metabolic disorders in horse muscles suffering from polysaccharide storage myopathy (PSSM), a condition where abnormal amounts of glycogen and its byproduct, polysaccharide, accumulate in muscle cells. Results showed evidence of inflammation, inhibited glycogenesis, hypoxia, and mitochondrial dysfunctions.

Research Methodology

  • A gene expression profiling was carried out on the muscles of Normand Cob breed horses with PSSM to understand the condition at the genetic level and its possible connection to gene dysfunctions.
  • The researchers employed a functional genomic approach to shed more light on the metabolic disorders relating to PSSM.
  • Massive amounts of abnormal polysaccharides, inflammation, muscle cell necrosis, lipomatosis, and active fiber regeneration were detected during histological examinations of PSSM muscle tissues.
  • Genotype analysis of GYS1 mutation was conducted revealing 2 horses with homozygous (AA) and 5 horses with heterozygous (GA) PSSM.
  • A decrease in the number of mitochondria and structural disorders were observed upon ultrastructural evaluation.

Research Findings

  • The severity of the PSSM was found to be higher in homozygous horses than in heterozygous horses.
  • There were 129 genes that significantly modulated; the most up-regulated ones were IL18, CTSS, LUM, CD44, FN1, GST01 and the most down-regulated ones included mitochondrial tRNA, SLC2A2, PRKCalpha, VEGFalpha.
  • Data analysis showed that protein synthesis, apoptosis, cellular movement, growth, and proliferation were the main cellular functions associated with the modulated genes.
  • Severe muscular inflammation in PSSM muscles was revealed by several up-regulated genes, especially IL18.
  • Glycogen synthase kinase-3 (GSK3beta) under its active form led to glycogen synthase (GYS1) inhibition and hypoxia-inducible factor (HIF1alpha) destabilization.

Conclusion

  • The scientists concluded that the main disorders observed in PSSM muscles could be associated with mitochondrial dysfunctions, glycogenesis inhibition, and chronic hypoxia of the PSSM muscles.

Cite This Article

APA
Barrey E, Mucher E, Jeansoule N, Larcher T, Guigand L, Herszberg B, Chaffaux S, Guérin G, Mata X, Benech P, Canale M, Alibert O, Maltere P, Gidrol X. (2009). Gene expression profiling in equine polysaccharide storage myopathy revealed inflammation, glycogenesis inhibition, hypoxia and mitochondrial dysfunctions. BMC Vet Res, 5, 29. https://doi.org/10.1186/1746-6148-5-29

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 5
Pages: 29

Researcher Affiliations

Barrey, Eric
  • Unité de Biologie Intégrative des Adaptations à l'Exercice -INSERM 902, Genopole Evry, France. eric.barrey@inserm.fr
Mucher, Elodie
    Jeansoule, Nicolas
      Larcher, Thibaut
        Guigand, Lydie
          Herszberg, Bérénice
            Chaffaux, Stéphane
              Guérin, Gérard
                Mata, Xavier
                  Benech, Philippe
                    Canale, Marielle
                      Alibert, Olivier
                        Maltere, Péguy
                          Gidrol, Xavier

                            MeSH Terms

                            • Animals
                            • Female
                            • Gene Expression Profiling
                            • Gene Expression Regulation
                            • Genotype
                            • Glycogen / metabolism
                            • Horse Diseases / physiopathology
                            • Horses
                            • Hypoxia / etiology
                            • Hypoxia / veterinary
                            • Inflammation / etiology
                            • Inflammation / physiopathology
                            • Male
                            • Mitochondria / pathology
                            • Muscle, Skeletal / physiopathology
                            • Muscular Diseases / complications
                            • Muscular Diseases / physiopathology
                            • Muscular Diseases / veterinary
                            • Phenotype
                            • Polysaccharides / metabolism

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