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Home / Equine Research Bank / Equine Vet J / Clinical and histopathological features of myofibrillar myop...
Equine veterinary journal2017; 49(6); 739-745; doi: 10.1111/evj.12702

Clinical and histopathological features of myofibrillar myopathy in Warmblood horses.

Abstract: To report a novel exertional myopathy, myofibrillar myopathy (MFM) in Warmblood (WB) horses. Objective: To 1) describe the distinctive clinical and myopathic features of MFM in Warmblood horses and 2) investigate the potential inheritance of MFM in a Warmblood family. Methods: Retrospective selection of MFM cases and prospective evaluation of a Warmblood family. Methods: Retrospectively, muscle biopsies were selected from Warmblood horses diagnosed with MFM and clinical histories obtained (n = 10). Prospectively, muscle biopsies were obtained from controls (n = 8) and a three generation WB family (n = 11). Samples were assessed for histopathology [scored 0-3], fibre types, cytoskeletal and Z disc protein aggregates, electron microscopic alterations (EM) and muscle glycogen concentrations. Results: Myofibrillar myopathy-affected cases experienced exercise intolerance, reluctance to go forward, stiffness and poorly localised lameness. Abnormal aggregates of the cytoskeletal protein desmin were found in up to 120 type 2a and a few type 2x myofibres of MFM cases. Desmin positive fibres did not stain for developmental myosin, α actinin or dystrophin. Scores for internalised myonuclei (score MFM 0.83 ± 0.67, controls 0.22 ± 0.45), anguloid atrophy (MFM 0.95 ± 0.55, controls 0.31 ± 0.37) and total myopathic scores (MFM 5.85 ± 2.10, controls 1.41 ± 2.17) were significantly higher in MFM cases vs. Methods: Focal Z disc degeneration, myofibrillar disruption and accumulation of irregular granular material was evident in MFM cases. Muscle glycogen concentrations were similar between MFM cases and controls. In the Warmblood family, desmin positive aggregates were found in myofibres of the founding dam and in horses from two subsequent generations. Conclusions: Restricted sample size due to limited availability of well phenotyped cases. Conclusions: A distinctive and potentially heritable form of MFM exists in Warmblood horses that present with exercise intolerance and abnormal hindlimb gait. Muscle tissue is characterised by ectopic accumulation of desmin and Z disc and myofibrillar degeneration.
© 2017 EVJ Ltd.
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Publication Date: 2017-06-26 PubMed ID: 28543538PubMed Central: PMC5640499DOI: 10.1111/evj.12702Google 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.

This research article studies a particular type of exertional myopathy, called myofibrillar myopathy (MFM), in Warmblood horses. It investigates both distinctive characteristics of MFM and its potential inheritance within a family of Warmblood horses.

Methods

The researchers used both retrospective and prospective methods to evaluate MFM in Warmblood horses. Retrospectively, the researchers colleted muscle biopsies from horses already diagnosed with MFM and studied their clinical histories. Prospectively, they collected muscle biopsies from a family of Warmblood horses across three generations. Both sets of biopsies were studied for several factors such as histopathology, fibre types, the presence of protein aggregates in the cytoskeleton and Z disc, alterations visible under electron microscope, and concentrations of muscle glycogen.

Results

Warmblood horses affected with MFM displayed exercise intolerance, stiffness, and reluctance to move forward, along with poorly localized lameness. Analyses of the biopsies revealed several abnormalities:

  • The presence of abnormal aggregates of a protein called desmin in up to 120 type 2a and a few type 2x myofibres.
  • Significantly higher scores for internalized myonuclei, anguloid atrophy and total myopathic scores in MFM cases compared to controls.
  • Evidence of Z disc degeneration, myofibrillar disruption, and accumulation of irregular granular material in MFM cases.

Muscle glycogen concentrations were found to be similar between MFM cases and controls.

In the studied Warmblood family, desmin positive aggregates were found in the muscles of the founding dam and horses from two subsequent generations, suggesting a possibly heritable nature of MFM.

Conclusions

The study concludes that a distinctive, potentially heritable form of MFM exists in Warmblood horses. This myopathy presents with symptoms like exercise intolerance and abnormal hindlimb gait. The affected muscle tissue is characterised by the abnormal accumulation of desmin and degeneration of Z disc and myofibrils. The study’s conclusions are limited by the small sample size.

Cite This Article

APA
Valberg SJ, Nicholson AM, Lewis SS, Reardon RA, Finno CJ. (2017). Clinical and histopathological features of myofibrillar myopathy in Warmblood horses. Equine Vet J, 49(6), 739-745. https://doi.org/10.1111/evj.12702

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 49
Issue: 6
Pages: 739-745

Researcher Affiliations

Valberg, S J
  • McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan, USA.
Nicholson, A M
  • Wilhite & Frees Equine Hospital, Peculiar, Missouri, USA.
Lewis, S S
  • Hagyard Equine Medical Institute, Lexington, Kentucky, USA.
Reardon, R A
  • West End Equine Veterinary Services, Inc., Delano, Minnesota, USA.
Finno, C J
  • Department of Population Health and Reproduction, University of California Davis, Davis, California, USA.

MeSH Terms

  • Animals
  • Female
  • Genetic Predisposition to Disease
  • Horse Diseases / genetics
  • Horse Diseases / pathology
  • Horses
  • Male
  • Myopathies, Structural, Congenital / genetics
  • Myopathies, Structural, Congenital / pathology
  • Myopathies, Structural, Congenital / veterinary

Grant Funding

  • K01 OD015134 / NIH HHS
  • L40 TR001136 / NCATS NIH HHS

Conflict of Interest Statement

Authors’ declaration of interests. S. Valberg and her colleagues license the PSSM1 genetic test mentioned in this paper and she receives royalties from the test.

References

This article includes 31 references
  1. Kold SE, Dyson SJ. Lameness in the dressage horse.. In: Ross MW, Dyson SJ, editors. Diagnosis and Management of Lameness in the Horse. 2nd. Elsevier Saunders; St. Louis, Missouri: 2011. pp. 112–1123.
  2. Murray RC, Walters JM, Snart H, Dyson SJ, Parkin TD. Identification of risk factors for lameness in dressage horses.. Vet J 2010;184:27–36.
    pubmed: 19369100
  3. Quiroz-Rothe E, Novales M, Guilera-Tejero E, Rivero JL. Polysaccharide storage myopathy in the M. longissimus lumborum of showjumpers and dressage horses with back pain.. Equine Vet J 2002;34:171–176.
    pubmed: 11905436
  4. Hunt LM, Valberg SJ, Steffenhagen K, McCue ME. An epidemiological study of myopathies in Warmblood horses.. Equine Vet J 2008;40:171–177.
    pubmed: 18089471
  5. Johlig L, Valberg SJ, Mickelson JR, Klukowska J, Reusser HR, Straub R, Gerber V. Epidemiological and genetic study of exertional rhabdomyolysis in a Warmblood horse family in Switzerland.. Equine Vet J 2011;43:240–245.
    pubmed: 21592222
  6. McCue ME, Valberg SJ, Miller MB, Wade C, DiMauro S, Akman HO, Mickelson JR. Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis.. Genomics 2008;91:458–466.
    pmc: PMC2430182pubmed: 18358695
  7. Valberg S. Muscling in on the cause of tying up.. Proc Am Ass Equine Practnrs 2012;58:85–123.
  8. Lewis SS, Nicholson AM, Williams Z, Valberg SJ. Warmblood horses with polysaccharide storage myopathy: clinical characteristics and muscle glycogen concentrations.. Am J Vet Res 2017 in press.
    pubmed: 29076373
  9. Valberg SJ, McKenzie EC, Eyrich LV, Shivers J, Barnes NE, Finno CJ. Suspected myofibrillar myopathy in Arabian horses with a history of exertional rhabdomyolysis.. Equine Vet J 2016;48:548–556.
    pmc: PMC4833696pubmed: 26234161
  10. McKenzie EC, Eyrich LV, Payton ME, Valberg SJ. Clinical, histopathological and metabolic responses following exercise in Arabian horses with a history of exertional rhabdomyolysis.. Vet J 2016;216:196–201.
    pubmed: 27687952
  11. Goldspink G. Cytological basis of decrease in muscle strength during starvation.. Am J Physiol 1965;209:100–104.
    pubmed: 14343743
  12. Lindholm A, Piehl K. Fibre composition, enzyme activity and concentrations of metabolites and electrolytes in muscles of standardbred horses.. Acta Vet Scand 1974;15:287–309.
    pmc: PMC8407315pubmed: 4137664
  13. Cumming WJK, Fulthorp JJ, Hudgson H, Mahon M. Color Atlas of Muscle Pathology.. Mosby-Wolfe; London: 1994. Histological and histochemical procedures; pp. 183–188.
  14. Brooke MH, Kaiser KK. Muscle fiber types: how many and what kind?. Arch Neurol 1970;23:369–379.
    pubmed: 4248905
  15. Lowry OH, Passonneau JV. A Flexible System for Enzyme Analysis.. Academic Press; New York: 1972. A kinetic primer for tissue analysts; pp. 21–25.
  16. Lunn DP, Mayhew IG. The neurologic evaluation of horses.. Equine Vet Educ 1989;1:94–101.
  17. Valberg SJ. Spinal muscle pathology.. Vet Clin N Am: Equine Pract 1999;15:87–96.
    pubmed: 10218243
  18. Dubowitz V, Sewry CA. Immunohistochemistry.. In: Dubowitz V, Sewry CA, editors. Muscle Biopsy; A Practical Approach. Saunders, Elsevier; Philadelphia: 2007. pp. 225–226.
  19. Barash IA, Peters D, Friden J, Lutz GJ, Lieber RL. Desmin cytoskeletal modifications after a bout of eccentric exercise in the rat.. Am J Physiol Regul Integr Comp Physiol 2002;283:R958–R963.
    pubmed: 12228066
  20. Lieber RL, Thornell LE, Fridén J. Muscle cytoskeleta disruption occurs within the first 15 min of cyclic eccentric contraction.. J Appl Physiol 1985;80:278–284.
    pubmed: 8847315
  21. Selcen D, Engel AG. Myofibrillar myopathies.. Handb Clin Neurol 2011;101:143–154.
    pubmed: 21496631
  22. Selcen D, Ohno K, Engel AG. Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients.. Brain 2004;127:439–451.
    pubmed: 14711882
  23. Claeys KG, van der Ven PF, Behin A, Stojkovic T, Eymard B, Dubourg O, Laforet P, Faulkner G, Richard P, Vicart P, Romero NB, Stoltenburg G, Udd B, Fardeau M, Voit T, Furst DO. Differential involvement of sarcomeric proteins in myofibrillar myopathies: a morphological and immunohistochemical study.. Acta Neuropathol 2009;117:293–307.
    pubmed: 19151983
  24. Claeys KG, Fardeau M, Schroder R, Suominen T, Tolksdorf K, Behin A, Dubourg O, Eymard B, Maisonobe T, Stojkovic T, Faulkner G, Richard P, Vicart P, Udd B, Voit T, Stoltenburg G. Electron microscopy in myofibrillar myopathies reveals clues to the mutated gene.. Neuromuscul. Disord. 2008;18:656–666.
    pubmed: 18653338
  25. Chevessier F, Schuld J, Orfanos Z, Plank AC, Wolf L, Maerkens A, Unger A, Schlotzer-Schrehardt U, Kley RA, Von Horsten S, Marcus K, Linke WA, Vorgerd M, van der Ven PF, Furst DO, Schroder R. Myofibrillar instability exacerbated by acute exercise in filaminopathy.. Hum Mol Genet 2015;24:7207–7220.
    pubmed: 26472074
  26. Kley RA, Hellenbroich Y, van der Ven PF, Furst DO, Huebner A, Bruchertseifer V, Peters SA, Heyer CM, Kirschner J, Schroder R, Fischer D, Muller K, Tolksdorf K, Eger K, Gerring A, Brodherr T, Reum C, Walter MC, Lochmuller H, Ketelsen UP, Vorgerd M. Clinical and morphological phenotype of the filamin myopathy: a study of 31 German patients.. Brain 2007;130:3250–3264.
    pubmed: 18055494
  27. De La Corte FD, Valberg SJ, MacLeay JM, Mickelson JR. Developmental onset of polysaccharide storage myopathy in 4 Quarter Horse foals.. J Vet Intern Med 2002;16:581–587.
    pubmed: 12322710
  28. McCue ME, Armien AG, Lucio M, Mickelson JR, Valberg SJ. Comparative skeletal muscle histopathologic and ultrastructural features in two forms of polysaccharide storage myopathy in horses.. Vet Pathol 2009;46:1281–1291.
    pubmed: 19605906
  29. Urschel KL, Escobar J, McCutcheon LJ, Geor RJ. Effect of feeding a high-protein diet following an 18-hour period of feed withholding on mammalian target of rapamycin-dependent signaling in skeletal muscle of mature horses.. Am J Vet Res 2011;72:248–255.
    pubmed: 21281201
  30. Graham-Thiers PM, Kronfeld DS. Amino acid supplementation improves muscle mass in aged and young horses.. J Anim Sci 2005;83:2783–2788.
    pubmed: 16282616
  31. Nguyen MT, Joya JE, Kee AJ, Domazetovska A, Yang N, Hook JW, Lemckert FA, Kettle E, Valova VA, Robinson PJ, North KN, Gunning PW, Mitchell CA, Hardeman EC. Hypertrophy and dietary tyrosine ameliorate the phenotypes of a mouse model of severe nemaline myopathy.. Brain 2011;134:3516–3529.
    pubmed: 22067542

Citations

This article has been cited 8 times.
  1. Lindsay-McGee V, Massey C, Li YT, Clark EL, Psifidi A, Piercy RJ. Characterisation of phenotypic patterns in equine exercise-associated myopathies. Equine Vet J 2025 Mar;57(2):347-361.
    doi: 10.1111/evj.14128pubmed: 38965932google scholar: lookup
  2. Valberg SJ, Velez-Irizarry D, Williams ZJ, Henry ML, Iglewski H, Herrick K, Fenger C. Enriched Pathways of Calcium Regulation, Cellular/Oxidative Stress, Inflammation, and Cell Proliferation Characterize Gluteal Muscle of Standardbred Horses between Episodes of Recurrent Exertional Rhabdomyolysis. Genes (Basel) 2022 Oct 14;13(10).
    doi: 10.3390/genes13101853pubmed: 36292738google scholar: lookup
  3. Valberg SJ, Henry ML, Herrick KL, Velez-Irizarry D, Finno CJ, Petersen JL. Absence of myofibrillar myopathy in Quarter Horses with a histopathological diagnosis of type 2 polysaccharide storage myopathy and lack of association with commercial genetic tests. Equine Vet J 2023 Mar;55(2):230-238.
    doi: 10.1111/evj.13574pubmed: 35288976google scholar: lookup
  4. Williams ZJ, Velez-Irizarry D, Gardner K, Valberg SJ. Integrated proteomic and transcriptomic profiling identifies aberrant gene and protein expression in the sarcomere, mitochondrial complex I, and the extracellular matrix in Warmblood horses with myofibrillar myopathy. BMC Genomics 2021 Jun 11;22(1):438.
    doi: 10.1186/s12864-021-07758-0pubmed: 34112090google scholar: lookup
  5. Valberg SJ, Finno CJ, Henry ML, Schott M, Velez-Irizarry D, Peng S, McKenzie EC, Petersen JL. Commercial genetic testing for type 2 polysaccharide storage myopathy and myofibrillar myopathy does not correspond to a histopathological diagnosis. Equine Vet J 2021 Jul;53(4):690-700.
    doi: 10.1111/evj.13345pubmed: 32896939google scholar: lookup
  6. Williams ZJ, Velez-Irizarry D, Petersen JL, Ochala J, Finno CJ, Valberg SJ. Candidate gene expression and coding sequence variants in Warmblood horses with myofibrillar myopathy. Equine Vet J 2021 Mar;53(2):306-315.
    doi: 10.1111/evj.13286pubmed: 32453872google scholar: lookup
  7. Valberg SJ, Perumbakkam S, McKenzie EC, Finno CJ. Proteome and transcriptome profiling of equine myofibrillar myopathy identifies diminished peroxiredoxin 6 and altered cysteine metabolic pathways. Physiol Genomics 2018 Dec 1;50(12):1036-1050.
    doi: 10.1152/physiolgenomics.00044.2018pubmed: 30289745google scholar: lookup
  8. Williams ZJ, Bertels M, Valberg SJ. Muscle glycogen concentrations and response to diet and exercise regimes in Warmblood horses with type 2 Polysaccharide Storage Myopathy. PLoS One 2018;13(9):e0203467.
    doi: 10.1371/journal.pone.0203467pubmed: 30183782google scholar: lookup
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