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Home / Equine Research Bank / Cells / Myofibre Hyper-Contractility in Horses Expressing the Myosin...
Cells2021; 10(12); 3428; doi: 10.3390/cells10123428

Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation, MYH1E321G.

Abstract: Myosinopathies are defined as a group of muscle disorders characterized by mutations in genes encoding myosin heavy chains. Their exact molecular and cellular mechanisms remain unclear. In the present study, we have focused our attention on a -related E321G amino acid substitution within the head region of the type IIx skeletal myosin heavy chain, associated with clinical signs of atrophy, inflammation and/or profound rhabdomyolysis, known as equine myosin heavy chain myopathy. We performed Mant-ATP chase experiments together with force measurements on isolated IIx myofibres from control horses () and Quarter Horses homozygous () or heterozygous () for the E321G mutation. The single residue replacement did not affect the relaxed conformations of myosin molecules. Nevertheless, it significantly increased its active behaviour as proven by the higher maximal force production and Ca sensitivity for in comparison with and horses. Altogether, these findings indicate that, in the presence of the E321G mutation, a molecular and cellular hyper-contractile phenotype occurs which could contribute to the development of the myosin heavy chain myopathy.
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Publication Date: 2021-12-06 PubMed ID: 34943936PubMed Central: PMC8699922DOI: 10.3390/cells10123428Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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 study outlines how a specific gene mutation, MYH1E321G, known to cause muscle disorders in horses, triggers over-contraction of muscle fibres potentially leading to equine myosin heavy chain myopathy.

Background

  • Myosinopathies are a group of muscle disorders that are caused by mutations in genes responsible for the production of myosin heavy chains, the engine of muscle contraction.
  • The underlying molecular and cellular mechanisms of these disorders are not fully understood.
  • The researchers in this study focus specifically on a mutation identified as MYH1E321G, located in the head region of type IIx skeletal myosin heavy chain. This mutation has been linked to clinical symptoms such as muscle wasting, inflammation, and severe muscle tissue breakdown (rhabdomyolysis), which are all indicative of a condition known as equine myosin heavy chain myopathy.

Methods

  • The team conducted Mant-ATP chase experiments and measured force on isolated type IIx myofibres from horses of different genetic make-ups – those without the mutation (control), horses that had two copies (homozygous) of the E321G mutation, and horses with just one copy (heterozygous) of the mutation.

Findings

  • The presence of the E321G mutation did not affect the usual relaxed configuration of myosin molecules in the muscle fibres.
  • The mutation, however, dramatically escalated the active behavior of myosin leading to an increased maximum force of muscle contraction and heightened sensitivity to calcium, a key player in muscle contraction, particularly in the homozygous horses compared to their control and heterozygous counterparts.

Conclusion

  • The study suggests that the MYH1E321G mutation results in a hyper-contractile phenotype at the molecular and cellular level. This over-contraction could be a significant factor in the onset of equine myosin heavy chain myopathy in affected horses.
  • The findings add to the current understanding of the mechanisms behind myosinopathies and could guide future research and therapeutic strategies targeting this group of muscle disorders in horses.

Cite This Article

APA
Ochala J, Finno CJ, Valberg SJ. (2021). Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation, MYH1E321G. Cells, 10(12), 3428. https://doi.org/10.3390/cells10123428

Publication

Cells
ISSN: 2073-4409
NlmUniqueID: 101600052
Country: Switzerland
Language: English
Volume: 10
Issue: 12
PII: 3428

Researcher Affiliations

Ochala, Julien
  • Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
  • Centre of Human and Applied Physiological Sciences, Faculty of Life Sciences & Medicine, School of Basic and Medical Biosciences, King's College London, London SE1 1UL, UK.
  • Randall Centre for Cell and Molecular Biophysics, Faculty of Life Sciences & Medicine, School of Basic & Medical Biosciences, King's College London, London SE1 1UL, UK.
Finno, Carrie J
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California at Davis, Davis, CA 95616, USA.
Valberg, Stephanie J
  • Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.

MeSH Terms

  • Amino Acid Substitution / genetics
  • Animals
  • Gene Expression Regulation / genetics
  • Heterozygote
  • Homozygote
  • Horses / genetics
  • Muscle Contraction / genetics
  • Muscle Contraction / physiology
  • Muscular Diseases / genetics
  • Muscular Diseases / pathology
  • Muscular Diseases / veterinary
  • Mutation / genetics
  • Myofibrils / genetics
  • Myofibrils / metabolism
  • Myosin Heavy Chains / genetics

Grant Funding

  • MR/S023593/1 / Medical Research Council

Conflict of Interest Statement

The authors declare no conflict of interest.

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