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Home / Equine Research Bank / Sci Rep / A highly prevalent SINE mutation in the myostatin (MSTN) gen...
Scientific reports2021; 11(1); 7916; doi: 10.1038/s41598-021-86783-1

A highly prevalent SINE mutation in the myostatin (MSTN) gene promoter is associated with low circulating myostatin concentration in Thoroughbred racehorses.

Abstract: Horse racing is a popular and financially important industry worldwide and researchers and horse owners are interested in genetic and training influences that maximise athletic performance. An association has been found between the presence of a short interspersed nuclear element (SINE) mutation in the myostatin (MSTN) gene promoter and optimal race distance in Thoroughbred horses. There is previous laboratory evidence that this mutation reduces MSTN expression in a cell culture model and influences skeletal muscle fibre type proportions in horses. Manipulating MSTN expression has been proposed for illicit gene doping in human and equine athletes and already, researchers have generated homozygous and heterozygous MSTN-null horse embryos following CRISPR/Cas9 editing at the equine MSTN locus and nuclear transfer, aiming artificially to enhance performance. To date however, the role of the naturally-occurring equine MSTN SINE mutation in vivo has remained unclear; here we hypothesised that it reduces, but does not ablate circulating myostatin expression. Following validation of an ELISA for detection of myostatin in equine serum and using residual whole blood and serum samples from 176 Thoroughbred racehorses under identical management, horses were genotyped for the SINE mutation by PCR and their serum myostatin concentrations measured. In our population, the proportions of SINE homozygotes, heterozygotes and normal horses were 27%, 46% and 27% respectively. Results indicated that horses that are homozygous for the SINE mutation have detectable, but significantly lower (p < 0.0001) serum myostatin concentrations (226.8 pg/ml; 69.3-895.4 pg/ml; median; minimum-maximum) than heterozygous (766 pg/ml; 64.6-1182 pg/ml) and normal horses (1099 pg/ml; 187.8-1743 pg/ml). Heterozygotes have significantly lower (p < 0.0001) myostatin concentrations than normal horses. Variation in serum myostatin concentrations across horses was not influenced by age or sex. This is the first study to reveal the direct functional effect of a highly prevalent mutation in the equine MSTN gene associated with exercise performance. Determining the reason for variation in expression of myostatin within SINE-genotyped groups might identify additional performance-associated environmental or genetic influences in Thoroughbreds. Understanding the mechanism by which altered myostatin expression influences skeletal muscle fibre type remains to be determined.
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Publication Date: 2021-04-12 PubMed ID: 33846367PubMed Central: PMC8041750DOI: 10.1038/s41598-021-86783-1Google 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 centers on the potential performance-enhancing role of a prevalent gene mutation in racehorses. The study found that a mutation in the myostatin (MSTN) gene promoter is associated with lower concentrations of circulating myostatin in Thoroughbred racehorses, which could influence muscle development and race performance.

Mutation in the Myostatin Gene

  • The study took a closer look at the Myostatin (MSTN) gene, which is significant in controlling muscle growth. An alteration or mutation in this gene, known as a SINE mutation, was found to be prevalent in Thoroughbred racehorses.
  • Previous lab results indicated that this mutation could reduce MSTN expression and alter the proportions of different types of muscle fibres in horses. This led the researchers to hypothesize that this mutation might potentially reduce myostatin concentration in the blood, but not fully eliminate it.

Influence on Race Performance

  • The findings from this research are particularly relevant for the horse racing industry as they could influence race performance. Genetic manipulation to reduce myostatin expression, either naturally or artificially, has been suggested as a means to enhance performance. Researchers have even managed to generate horse embryos with no MSTN expression using genetic editing and nuclear transfer techniques.
  • In their test population of 176 Thoroughbred racehorses, they found varying proportions of horses with homozygote, heterozygote, and normal SINE genes. Importantly, the horses with the homozygous SINE mutation had substantially lower levels of myostatin in their serum.
  • This information propels the potential for genetic influences on race performance and reaffirms the need for additional research into possible performance-related environmental or genetic influences.

Study Outcomes and Future Research

  • The research revealed that horses with the homozygous SINE mutation had lower serum myostatin concentrations without being influenced by the age or sex of the horses.
  • While this is the first study of its kind to reveal the functional impact of this prevalent mutation on equine performance, further research is required to discern the exact mechanism through which altered myostatin expression influences the type of muscle fibres, and thereby horse performance.

Cite This Article

APA
O'Hara V, Cowan A, Riddell D, Massey C, Martin J, Piercy RJ. (2021). A highly prevalent SINE mutation in the myostatin (MSTN) gene promoter is associated with low circulating myostatin concentration in Thoroughbred racehorses. Sci Rep, 11(1), 7916. https://doi.org/10.1038/s41598-021-86783-1

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 11
Issue: 1
Pages: 7916
PII: 7916

Researcher Affiliations

O'Hara, Victoria
  • Comparative Neuromuscular Diseases Laboratory, Department of Veterinary Clinical Sciences, Royal Veterinary College, Royal College Street, London, UK.
Cowan, Amélie
  • Comparative Neuromuscular Diseases Laboratory, Department of Veterinary Clinical Sciences, Royal Veterinary College, Royal College Street, London, UK.
Riddell, Dominique
  • Comparative Neuromuscular Diseases Laboratory, Department of Veterinary Clinical Sciences, Royal Veterinary College, Royal College Street, London, UK.
Massey, Claire
  • Comparative Neuromuscular Diseases Laboratory, Department of Veterinary Clinical Sciences, Royal Veterinary College, Royal College Street, London, UK.
Martin, John
  • Johnston Racing, Kingsley Park, Middleham, Leyburn, UK.
Piercy, Richard J
  • Comparative Neuromuscular Diseases Laboratory, Department of Veterinary Clinical Sciences, Royal Veterinary College, Royal College Street, London, UK. rpiercy@rvc.ac.uk.

MeSH Terms

  • Animals
  • Female
  • Genotype
  • Horses / blood
  • Horses / genetics
  • Male
  • Mutation / genetics
  • Myostatin / blood
  • Myostatin / genetics
  • Promoter Regions, Genetic
  • Short Interspersed Nucleotide Elements / genetics

Conflict of Interest Statement

The authors declare no competing interests.

References

This article includes 39 references
  1. Beyer TA, Narimatsu M, Weiss A, David L, Wrana JL. The TGFβ superfamily in stem cell biology and early mammalian embryonic development.. Biochim Biophys Acta 2013 Feb;1830(2):2268-79.
    doi: 10.1016/j.bbagen.2012.08.025pubmed: 22967760google scholar: lookup
  2. Trendelenburg AU, Meyer A, Rohner D, Boyle J, Hatakeyama S, Glass DJ. Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size.. Am J Physiol Cell Physiol 2009 Jun;296(6):C1258-70.
    doi: 10.1152/ajpcell.00105.2009pubmed: 19357233google scholar: lookup
  3. Matsakas A, Otto A, Elashry MI, Brown SC, Patel K. Altered primary and secondary myogenesis in the myostatin-null mouse.. Rejuvenation Res 2010 Dec;13(6):717-27.
    doi: 10.1089/rej.2010.1065pubmed: 21204650google scholar: lookup
  4. Hill EW, McGivney BA, Rooney MF, Katz LM, Parnell A, MacHugh DE. The contribution of myostatin (MSTN) and additional modifying genetic loci to race distance aptitude in Thoroughbred horses racing in different geographic regions.. Equine Vet J 2019 Sep;51(5):625-633.
    doi: 10.1111/evj.13058pubmed: 30604488google scholar: lookup
  5. Aiello D, Patel K, Lasagna E. The myostatin gene: an overview of mechanisms of action and its relevance to livestock animals.. Anim Genet 2018 Dec;49(6):505-519.
    doi: 10.1111/age.12696pubmed: 30125951google scholar: lookup
  6. Brzeziańska E, Domańska D, Jegier A. Gene doping in sport - perspectives and risks.. Biol Sport 2014 Dec;31(4):251-9.
    doi: 10.5604/20831862.1120931pmc: PMC4203840pubmed: 25435666google scholar: lookup
  7. Tozaki T, Ohnuma A, Kikuchi M, Ishige T, Kakoi H, Hirota KI, Hamilton NA, Kusano K, Nagata SI. Whole-genome resequencing using genomic DNA extracted from horsehair roots for gene-doping control in horse sports.. J Equine Sci 2020;31(4):75-83.
    doi: 10.1294/jes.31.75pmc: PMC7750640pubmed: 33376443google scholar: lookup
  8. Moro LN, Viale DL, Bastón JI, Arnold V, Suvá M, Wiedenmann E, Olguín M, Miriuka S, Vichera G. Generation of myostatin edited horse embryos using CRISPR/Cas9 technology and somatic cell nuclear transfer.. Sci Rep 2020 Sep 24;10(1):15587.
    doi: 10.1038/s41598-020-72040-4pmc: PMC7518276pubmed: 32973188google scholar: lookup
  9. Petersen JL, Mickelson JR, Rendahl AK, Valberg SJ, Andersson LS, Axelsson J, Bailey E, Bannasch D, Binns MM, Borges AS, Brama P, da Câmara Machado A, Capomaccio S, Cappelli K, Cothran EG, Distl O, Fox-Clipsham L, Graves KT, Guérin G, Haase B, Hasegawa T, Hemmann K, Hill EW, Leeb T, Lindgren G, Lohi H, Lopes MS, McGivney BA, Mikko S, Orr N, Penedo MC, Piercy RJ, Raekallio M, Rieder S, Røed KH, Swinburne J, Tozaki T, Vaudin M, Wade CM, McCue ME. Genome-wide analysis reveals selection for important traits in domestic horse breeds.. PLoS Genet 2013;9(1):e1003211.
    doi: 10.1371/journal.pgen.1003211pmc: PMC3547851pubmed: 23349635google scholar: lookup
  10. Hill EW, Gu J, Eivers SS, Fonseca RG, McGivney BA, Govindarajan P, Orr N, Katz LM, MacHugh DE. A sequence polymorphism in MSTN predicts sprinting ability and racing stamina in thoroughbred horses.. PLoS One 2010 Jan 20;5(1):e8645.
    doi: 10.1371/journal.pone.0008645pmc: PMC2808334pubmed: 20098749google scholar: lookup
  11. Bower MA, McGivney BA, Campana MG, Gu J, Andersson LS, Barrett E, Davis CR, Mikko S, Stock F, Voronkova V, Bradley DG, Fahey AG, Lindgren G, MacHugh DE, Sulimova G, Hill EW. The genetic origin and history of speed in the Thoroughbred racehorse.. Nat Commun 2012 Jan 24;3:643.
    doi: 10.1038/ncomms1644pubmed: 22273681google scholar: lookup
  12. Hill EW, Ryan DP, MacHugh DE. Horses for courses: a DNA-based test for race distance aptitude in thoroughbred racehorses.. Recent Pat DNA Gene Seq 2012 Dec;6(3):203-8.
    doi: 10.2174/187221512802717277pubmed: 22845060google scholar: lookup
  13. Serpa PB, Garbade P, Natalini CC, Pires AR, Tisotti TM. High-resolution melting analysis for detection of a single-nucleotide polymorphism and the genotype of the myostatin gene in warmblood horses.. Am J Vet Res 2017 Jan;78(1):63-68.
    doi: 10.2460/ajvr.78.1.63pubmed: 28029290google scholar: lookup
  14. Padilha FGF, El-Jaick KB, de Castro L, Moreira ADS, Ferreira AMR. Effect of selection for eventing on the MSTN gene in Brazilian sport horses.. J Equine Sci 2018;29(1):21-24.
    doi: 10.1294/jes.29.21pmc: PMC5865066pubmed: 29593445google scholar: lookup
  15. Dall'Olio S, Scotti E, Fontanesi L, Tassinari M. Analysis of the 227 bp short interspersed nuclear element (SINE) insertion of the promoter of the myostatin (MSTN) gene in different horse breeds.. Vet Ital 2014 Jul-Sep;50(3):193-7.
    doi: 10.12834/VetIt.61.178.3pubmed: 25273961google scholar: lookup
  16. Petersen JL, Valberg SJ, Mickelson JR, McCue ME. Haplotype diversity in the equine myostatin gene with focus on variants associated with race distance propensity and muscle fiber type proportions.. Anim Genet 2014 Dec;45(6):827-35.
    doi: 10.1111/age.12205pmc: PMC4211974pubmed: 25160752google scholar: lookup
  17. Rooney MF, Hill EW, Kelly VP, Porter RK. The "speed gene" effect of myostatin arises in Thoroughbred horses due to a promoter proximal SINE insertion.. PLoS One 2018;13(10):e0205664.
    doi: 10.1371/journal.pone.0205664pmc: PMC6209199pubmed: 30379863google scholar: lookup
  18. Santagostino M, Khoriauli L, Gamba R, Bonuglia M, Klipstein O, Piras FM, Vella F, Russo A, Badiale C, Mazzagatti A, Raimondi E, Nergadze SG, Giulotto E. Genome-wide evolutionary and functional analysis of the Equine Repetitive Element 1: an insertion in the myostatin promoter affects gene expression.. BMC Genet 2015 Oct 26;16:126.
    doi: 10.1186/s12863-015-0281-1pmc: PMC4623272pubmed: 26503543google scholar: lookup
  19. Kambadur R, Sharma M, Smith TP, Bass JJ. Mutations in myostatin (GDF8) in double-muscled Belgian Blue and Piedmontese cattle.. Genome Res 1997 Sep;7(9):910-6.
    doi: 10.1101/gr.7.9.910pubmed: 9314496google scholar: lookup
  20. McPherron AC, Lee SJ. Double muscling in cattle due to mutations in the myostatin gene.. Proc Natl Acad Sci U S A 1997 Nov 11;94(23):12457-61.
    doi: 10.1073/pnas.94.23.12457pmc: PMC24998pubmed: 9356471google scholar: lookup
  21. Deveaux V, Cassar-Malek I, Picard B. Comparison of contractile characteristics of muscle from Holstein and double-muscled Belgian Blue foetuses.. Comp Biochem Physiol A Mol Integr Physiol 2001 Dec;131(1):21-9.
    doi: 10.1016/S1095-6433(01)00459-7pubmed: 11733163google scholar: lookup
  22. Mosher DS, Quignon P, Bustamante CD, Sutter NB, Mellersh CS, Parker HG, Ostrander EA. A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs.. PLoS Genet 2007 May 25;3(5):e79.
    doi: 10.1371/journal.pgen.0030079pmc: PMC1877876pubmed: 17530926google scholar: lookup
  23. Morrison PK, Bing C, Harris PA, Maltin CA, Grove-White D, Argo CM. Preliminary investigation into a potential role for myostatin and its receptor (ActRIIB) in lean and obese horses and ponies.. PLoS One 2014;9(11):e112621.
    doi: 10.1371/journal.pone.0112621pmc: PMC4229217pubmed: 25390640google scholar: lookup
  24. Tanaka M, Masuda S, Yamakage H, Inoue T, Ohue-Kitano R, Yokota S, Kusakabe T, Wada H, Sanada K, Ishii K, Hasegawa K, Shimatsu A, Satoh-Asahara N. Role of serum myostatin in the association between hyperinsulinemia and muscle atrophy in Japanese obese patients.. Diabetes Res Clin Pract 2018 Aug;142:195-202.
    doi: 10.1016/j.diabres.2018.05.041pubmed: 29859272google scholar: lookup
  25. Peng LN, Lee WJ, Liu LK, Lin MH, Chen LK. Healthy community-living older men differ from women in associations between myostatin levels and skeletal muscle mass.. J Cachexia Sarcopenia Muscle 2018 Aug;9(4):635-642.
    doi: 10.1002/jcsm.12302pmc: PMC6104118pubmed: 29654636google scholar: lookup
  26. Yano S, Nagai A, Isomura M, Yamasaki M, Kijima T, Takeda M, Hamano T, Nabika T. Relationship between Blood Myostatin Levels and Kidney Function:Shimane CoHRE Study.. PLoS One 2015;10(10):e0141035.
    doi: 10.1371/journal.pone.0141035pmc: PMC4621051pubmed: 26502079google scholar: lookup
  27. Poggioli T, Vujic A, Yang P, Macias-Trevino C, Uygur A, Loffredo FS, Pancoast JR, Cho M, Goldstein J, Tandias RM, Gonzalez E, Walker RG, Thompson TB, Wagers AJ, Fong YW, Lee RT. Circulating Growth Differentiation Factor 11/8 Levels Decline With Age.. Circ Res 2016 Jan 8;118(1):29-37.
    doi: 10.1161/CIRCRESAHA.115.307521pmc: PMC4748736pubmed: 26489925google scholar: lookup
  28. White TA, LeBrasseur NK. Myostatin and sarcopenia: opportunities and challenges - a mini-review.. Gerontology 2014;60(4):289-93.
    doi: 10.1159/000356740pubmed: 24457615google scholar: lookup
  29. Arrieta H, Hervás G, Rezola-Pardo C, Ruiz-Litago F, Iturburu M, Yanguas JJ, Gil SM, Rodriguez-Larrad A, Irazusta J. Serum Myostatin Levels Are Higher in Fitter, More Active, and Non-Frail Long-Term Nursing Home Residents and Increase after a Physical Exercise Intervention.. Gerontology 2019;65(3):229-239.
    doi: 10.1159/000494137pubmed: 30463070google scholar: lookup
  30. Wu LF, Zhu DC, Wang BH, Lu YH, He P, Zhang YH, Gao HQ, Zhu XW, Xia W, Zhu H, Mo XB, Lu X, Zhang L, Zhang YH, Deng FY, Lei SF. Relative abundance of mature myostatin rather than total myostatin is negatively associated with bone mineral density in Chinese.. J Cell Mol Med 2018 Feb;22(2):1329-1336.
    doi: 10.1111/jcmm.13438pmc: PMC5783859pubmed: 29247983google scholar: lookup
  31. Koyun D, Nergizoglu G, Kir KM. Evaluation of the relationship between muscle mass and serum myostatin levels in chronic hemodialysis patients.. Saudi J Kidney Dis Transpl 2018 Jul-Aug;29(4):809-815.
    doi: 10.4103/1319-2442.239648pubmed: 30152416google scholar: lookup
  32. Ma Y, Li X, Zhang H, Ou Y, Zhang Z, Li S, Wu F, Sheng Z, Liao E. Serum myostatin in central south Chinese postmenopausal women: Relationship with body composition, lipids and bone mineral density.. Endocr Res 2016 Aug;41(3):223-8.
    doi: 10.3109/07435800.2015.1044609pubmed: 27144806google scholar: lookup
  33. Binns A, Gray M, Henson AC, Fort IL. Changes in Lean Mass and Serum Myostatin with Habitual Protein Intake and High-Velocity Resistance Training.. J Nutr Health Aging 2017;21(10):1111-1117.
    doi: 10.1007/s12603-017-0883-6pubmed: 29188869google scholar: lookup
  34. Farries G, Gough KF, Parnell AC, McGivney BA, McGivney CL, McGettigan PA, MacHugh DE, Katz LM, Hill EW. Analysis of genetic variation contributing to measured speed in Thoroughbreds identifies genomic regions involved in the transcriptional response to exercise.. Anim Genet 2019 Dec;50(6):670-685.
    doi: 10.1111/age.12848pubmed: 31508842google scholar: lookup
  35. Tozaki T, Sato F, Hill EW, Miyake T, Endo Y, Kakoi H, Gawahara H, Hirota K, Nakano Y, Nambo Y, Kurosawa M. Sequence variants at the myostatin gene locus influence the body composition of Thoroughbred horses.. J Vet Med Sci 2011 Dec;73(12):1617-24.
    doi: 10.1292/jvms.11-0295pubmed: 21836385google scholar: lookup
  36. Schuelke M, Wagner KR, Stolz LE, Hübner C, Riebel T, Kömen W, Braun T, Tobin JF, Lee SJ. Myostatin mutation associated with gross muscle hypertrophy in a child.. N Engl J Med 2004 Jun 24;350(26):2682-8.
    doi: 10.1056/NEJMoa040933pubmed: 15215484google scholar: lookup
  37. Kawao N, Kaji H. Interactions between muscle tissues and bone metabolism.. J Cell Biochem 2015 May;116(5):687-95.
    doi: 10.1002/jcb.25040pubmed: 25521430google scholar: lookup
  38. Dankbar B, Fennen M, Brunert D, Hayer S, Frank S, Wehmeyer C, Beckmann D, Paruzel P, Bertrand J, Redlich K, Koers-Wunrau C, Stratis A, Korb-Pap A, Pap T. Myostatin is a direct regulator of osteoclast differentiation and its inhibition reduces inflammatory joint destruction in mice.. Nat Med 2015 Sep;21(9):1085-90.
    doi: 10.1038/nm.3917pubmed: 26236992google scholar: lookup
  39. Tarantino U, Scimeca M, Piccirilli E, Tancredi V, Baldi J, Gasbarra E, Bonanno E. Sarcopenia: a histological and immunohistochemical study on age-related muscle impairment.. Aging Clin Exp Res 2015 Oct;27 Suppl 1:S51-60.
    doi: 10.1007/s40520-015-0427-zpubmed: 26197719google scholar: lookup

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  1. Budsuren U, Ulaangerel T, Shen Y, Liu G, Davshilt T, Yi M, Bold D, Zhang X, Bai D, Dorjgotov D, Davaakhuu G, Jambal T, Li B, Du M, Dugarjav M, Bou G. MSTN Regulatory Network in Mongolian Horse Muscle Satellite Cells Revealed with miRNA Interference Technologies. Genes (Basel) 2022 Oct 11;13(10).
    doi: 10.3390/genes13101836pubmed: 36292721google scholar: lookup
  2. Bruno S, Landi V, Senczuk G, Brooks SA, Almathen F, Faye B, Gaouar SSB, Piro M, Kim KS, David X, Eggen A, Burger P, Ciani E. Refining the Camelus dromedarius Myostatin Gene Polymorphism through Worldwide Whole-Genome Sequencing. Animals (Basel) 2022 Aug 14;12(16).
    doi: 10.3390/ani12162068pubmed: 36009658google scholar: lookup
  3. Samali SA, Hosseini SF, Mohammadi Y, Sadri F, Rezaei Z. Myostatin inhibitors in sarcopenia treatment: A comprehensive review of mechanisms, efficacy and future directions. Mol Biol Rep 2025 Dec 29;53(1):224.
    doi: 10.1007/s11033-025-11390-6pubmed: 41460393google scholar: lookup
  4. Hanousek K, O'Hara V, Riddell DO, Piercy RJ. Temporal and intra-horse consistency of circulating myostatin concentrations in Thoroughbred racehorses. Sci Rep 2025 Nov 5;15(1):38708.
    doi: 10.1038/s41598-025-22472-7pubmed: 41193553google scholar: lookup
  5. Borok MJ, Zaidan L, Relaix F. Transposon expression and repression in skeletal muscle. Mob DNA 2025 Apr 11;16(1):18.
    doi: 10.1186/s13100-025-00352-1pubmed: 40217332google scholar: lookup
  6. Yokomori T, Tozaki T, Segawa T, Itou T. Genomic regions and candidate genes associated with forehead whorl positioning in Thoroughbred horses. J Equine Sci 2025;36(1):11-18.
    doi: 10.1294/jes.36.11pubmed: 40115733google scholar: lookup
  7. Ayuti SR, Lamid M, Warsito SH, Al-Arif MA, Lokapirnasari WP, Rosyada ZNA, Sugito S, Akmal M, Rimayanti R, Gangil R, Khairullah AR, Abuzahra M, Moses IB, Anggraini L. A review of myostatin gene mutations: Enhancing meat production and potential in livestock genetic selection. Open Vet J 2024 Dec;14(12):3189-3202.
    doi: 10.5455/OVJ.2024.v14.i12.4pubmed: 39927343google scholar: lookup
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