OMIA:000683-9940 : Muscular hypertrophy (double muscling) in Ovis aries (sheep)

In other species: Japanese flounder , rock pigeon , chicken , dog , pig , taurine cattle , goat , rabbit , water buffalo , Japanese quail , yellow catfish

Categories: Muscle phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 601788 (gene) , 614160 (trait)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2006

Cross-species summary: Abnormal increase in muscular tissue caused entirely by enlargement of existing cells (in contrast to muscular hyperplasia, in which the abnormal increase in muscular tissue is due to the formation and growth of new, normal muscle cells)

Species-specific description: Information presented here was previously listed under OMIA:001426-9940 Muscular hypertrophy (double muscling), Texel In addition to the occurrence of natural variants for this trait, variants have been created artificially: Genetically-modifed organism; GMO. For other forms of muscular hypertrophy in sheep see: OMIA 001355-9940:Muscular hypertrophy (double muscling), Carwell OMIA 001354-9940:Muscular hypertrophy (double muscling), Callipyge

Molecular basis: In uncovering a previously-unrecognised source of variation, Clop et al. (2006) reported : "We herein demonstrate that the GDF8 allele of Texel sheep is characterized by a G to A transition in the 3' UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs) that are highly expressed in skeletal muscle. This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep. Analysis of SNP databases for humans and mice demonstrates that mutations creating or destroying putative miRNA target sites are abundant and might be important effectors of phenotypic variation." GDF8 is now known as MSTN (myostatin), and the mutation is g+6223G>A; c.*1232G>A. Hu et al. (2013) showed that "Knockdown of myostatin expression by RNAi enhances muscle growth in transgenic sheep". Haynes et al. (2013) reported that "lambs homozygous for the MSTN g+6723G>A mutation have changes in carcass characteristics (dressing and total lean), organ weights, and muscle fiber number. This may be due to reduced myostatin protein early in utero, but after 4 wk of age there was no difference in the abundance of mature myostatin protein in muscle or plasma among MSTN A/A, MSTN A/G, and MSTN G/G genotypes."

Genetic engineering: Yes - in addition to the occurrence of natural variants, variants have been created artificially, e.g. by genetic engineering or gene editing
Have human generated variants been created, e.g. through genetic engineering and gene editing

Prevalence: Kijas et al. (2007) reported that the favourable allele (g+6723A) "is near fixation within Australian Texels and present in additional breeds including White Suffolk, Poll Dorset and Lincoln" and that the direction and size of allele effect was very similar to that in the original Belgian Texel report by Clop et al. (2006). Bignall et al. (2010) reported the same allele in East Friesian sheep. Han et al. (2013) reported 28 nucleotide substitutions within the MSTN gene in "a diverse range of sheep breeds including the New Zealand (NZ) Romney, Coopworth, Corriedale, Dorper, Perendale, Suffolk, Merino, Dorset Down, Poll Dorset, Texel and other NZ cross-bred sheep."

Breeds: Charollais (Sheep) (VBO_0001368), Lincoln Longwool (Sheep) (VBO_0001490), Poll Dorset (Sheep) (VBO_0001557), Texel (Sheep) (VBO_0001641), White Suffolk, Australia (Sheep) (VBO_0015632).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MSTN myostatin Ovis aries 2 NC_056055.1 (119285858..119292614) MSTN Homologene, Ensembl , NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
435 Texel (Sheep) Muscular hypertrophy (double muscling), Texel MSTN regulatory Naturally occurring variant Oar_rambouillet_v1.0 2 g.129065977G>A c.*1232G>A "G to A transition in the 3' UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs)" rs408469734 2006 16751773 The genomic location on Oar_rambouillet_v1.0 was determined by Katie Eager, EMAI, NSW Department of Primary Industries.

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:000683-9940: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2024 García-Macia, M., Sierra, V., Santos-Ledo, A., de Luxán-Delgado, B., Potes-Ochoa, Y., Rodríguez-González, S., Oliván, M., Coto-Montes, A. :
Muscle hypertrophy is linked to changes in the oxidative and proteolytic systems during early tenderization of the Spanish breed "Asturiana de los Valles". Foods 13:443, 2024. Pubmed reference: 38338578. DOI: 10.3390/foods13030443.
Pan, Y., Li, S., Zhang, Q., Li, J., Song, C., Kong, L., Liu, Y., Hou, S., Li, S., Liu, Q., Xia, D., Wang, Z. :
Production performance analysis of sheep MSTN gene C2361T locus. J Genet Eng Biotechnol 22:S1687-157X(24)00075-1:100372, 2024. Pubmed reference: 38797546. DOI: 10.1016/j.jgeb.2024.100372.
Talebi, R., Mardi, M., Zeinalabedini, M., Kazemi Alamouti, M., Fabre, S., Ghaffari, M.R. :
Assessing the performance of Moghani crossbred lambs derived from different mating systems with Texel and Booroola sheep. PLoS One 19:e0301629, 2024. Pubmed reference: 38573987. DOI: 10.1371/journal.pone.0301629.
2023 Chen, M., Lian, D., Li, Y., Zhao, Y., Xu, X., Liu, Z., Zhang, J., Zhang, X., Wu, S., Qi, S., Deng, S., Yu, K., Lian, Z. :
Global long noncoding RNA expression profiling of MSTN and FGF5 double-knockout sheep reveals the key gatekeepers of skeletal muscle development. DNA Cell Biol 42:163-175, 2023. Pubmed reference: 36917699. DOI: 10.1089/dna.2022.0574.
Chen, M., Zhao, Y., Li, Y., Chen, T., Zhou, W., Zhang, X., Deng, S., Xu, X., Wu, S., Liu, Z., Qi, S., Wang, L., Li, Y., Yu, K., Lian, Z. :
Reproduction and viscera organ characteristics of MSTN and FGF5 dual-gene knockout sheep. Front Vet Sci 10:1119312, 2023. Pubmed reference: 37065235. DOI: 10.3389/fvets.2023.1119312.
Guo, R., Wang, H., Meng, C., Gui, H., Li, Y., Chen, F., Zhang, C., Zhang, H., Ding, Q., Zhang, J., Zhang, J., Qian, Y., Zhong, J., Cao, S. :
Efficient and specific generation of MSTN-edited Hu sheep using C-CRISPR. Genes (Basel) 14:1216, 2023. Pubmed reference: 37372396. DOI: 10.3390/genes14061216.
Kalds, P., Zhou, S., Huang, S., Gao, Y., Wang, X., Chen, Y. :
When less is more: Targeting the myostatin gene in livestock for augmenting meat production. J Agric Food Chem 71:4216-4227, 2023. Pubmed reference: 36862946. DOI: 10.1021/acs.jafc.2c08583.
2022 Zhou, S., Kalds, P., Luo, Q., Sun, K., Zhao, X., Gao, Y., Cai, B., Huang, S., Kou, Q., Petersen, B., Chen, Y., Ma, B., Wang, X. :
Optimized Cas9:sgRNA delivery efficiently generates biallelic MSTN knockout sheep without affecting meat quality. BMC Genomics 23:348, 2022. Pubmed reference: 35524183. DOI: 10.1186/s12864-022-08594-6.
2020 Menchaca, A., Dos Santos-Neto, P.C., Mulet, A.P., Crispo, M. :
CRISPR in livestock: From editing to printing. Theriogenology 150:247-254, 2020. Pubmed reference: 32088034. DOI: 10.1016/j.theriogenology.2020.01.063.
2019 Grochowska, E., Borys, B., Lisiak, D., Mroczkowski, S. :
Genotypic and allelic effects of the myostatin gene (MSTN) on carcass, meat quality, and biometric traits in Colored Polish Merino sheep. Meat Sci 151:4-17, 2019. Pubmed reference: 30658164. DOI: 10.1016/j.meatsci.2018.12.010.
2018 Aiello, D., Patel, K., Lasagna, E. :
The myostatin gene: an overview of mechanisms of action and its relevance to livestock animals. Anim Genet 49:505-19, 2018. Pubmed reference: 30125951. DOI: 10.1111/age.12696.
Freking, B.A., King, D.A., Shackelford, S.D., Wheeler, T.L., Smith, T.P.L. :
Effects and interactions of myostatin and callipyge mutations: I. Growth and carcass traits. J Anim Sci 96:454-461, 2018. Pubmed reference: 29401324. DOI: 10.1093/jas/skx055.
2016 Li, H., Wang, G., Hao, Z., Zhang, G., Qing, Y., Liu, S., Qing, L., Pan, W., Chen, L., Liu, G., Zhao, R., Jia, B., Zeng, L., Guo, J., Zhao, L., Zhao, H., Lv, C., Xu, K., Cheng, W., Li, H., Zhao, H.Y., Wang, W., Wei, H.J. :
Generation of biallelic knock-out sheep via gene-editing and somatic cell nuclear transfer. Sci Rep 6:33675, 2016. Pubmed reference: 27654750. DOI: 10.1038/srep33675.
Wang, X., Niu, Y., Zhou, J., Yu, H., Kou, Q., Lei, A., Zhao, X., Yan, H., Cai, B., Shen, Q., Zhou, S., Zhu, H., Zhou, G., Niu, W., Hua, J., Jiang, Y., Huang, X., Ma, B., Chen, Y. :
Multiplex gene editing via CRISPR/Cas9 exhibits desirable muscle hypertrophy without detectable off-target effects in sheep. Sci Rep 6:32271, 2016. Pubmed reference: 27562433. DOI: 10.1038/srep32271.
2013 Han, J., Forrest, R.H., Hickford, J.G. :
Genetic variations in the myostatin gene (MSTN) in New Zealand sheep breeds. Mol Biol Rep 40:6379-84, 2013. Pubmed reference: 24081623. DOI: 10.1007/s11033-013-2752-7.
Haynes, F.E., Greenwood, P.L., McDonagh, M.B., McMahon, C.D., Nicholas, G.D., Berry, C.J., Oddy, V.H. :
Lack of association between allelic status and myostatin content in lambs with the myostatin g+6723G>A allele. J Anim Sci 91:78-89, 2013. Pubmed reference: 23048142. DOI: 10.2527/jas.2012-5482.
Hu, S., Ni, W., Sai, W., Zi, H., Qiao, J., Wang, P., Sheng, J., Chen, C. :
Knockdown of myostatin expression by RNAi enhances muscle growth in transgenic sheep. PLoS One 8:e58521, 2013. Pubmed reference: 23526994. DOI: 10.1371/journal.pone.0058521.
Liu, C., Li, W., Zhang, X., Zhang, N., He, S., Huang, J., Ge, Y., Liu, M. :
Knockdown of endogenous myostatin promotes sheep myoblast proliferation. In Vitro Cell Dev Biol Anim 50:94-102, 2013. Pubmed reference: 24052475. DOI: 10.1007/s11626-013-9689-y.
Zhang, C., Wang, L., Ren, G., Li, Z., Ren, C., Zhang, T., Xu, K., Zhang, Z. :
Targeted disruption of the sheep MSTN gene by engineered zinc-finger nucleases. Mol Biol Rep 41:209-15, 2013. Pubmed reference: 24197697. DOI: 10.1007/s11033-013-2853-3.
2012 Haynes, F.E., Greenwood, P.L., McDonagh, M.B., Oddy, V.H. :
Myostatin allelic status interacts with level of nutrition to affect growth, composition, and myofiber characteristics of lambs. J Anim Sci 90:456-65, 2012. Pubmed reference: 21926323. DOI: 10.2527/jas.2011-4452.
Liu, C., Li, W., Zhang, X., Zhang, N., He, S., Huang, J., Ge, Y., Liu, M. :
The critical role of myostatin in differentiation of sheep myoblasts. Biochem Biophys Res Commun 422:381-6, 2012. Pubmed reference: 22580276. DOI: 10.1016/j.bbrc.2012.04.151.
Lu, J., Sun, D., Xu, L., Lu, G., Zhao, F., Wei, C., Zhang, L., Ding, J., Li, B., Du, L. :
Selection of an effective small interference RNA to silence myostatin gene expression in sheep fibroblast cells. Biochem Genet 50:838-47, 2012. Pubmed reference: 22736258. DOI: 10.1007/s10528-012-9524-2.
Tang, D., Zhu, H., Wu, J., Chen, H., Zhang, Y., Zhao, X., Chen, X., Du, W., Wang, D., Lin, X. :
Silencing myostatin gene by RNAi in sheep embryos. J Biotechnol 158:69-74, 2012. Pubmed reference: 22285957. DOI: 10.1016/j.jbiotec.2012.01.008.
Tellam, R.L., Cockett, N.E., Vuocolo, T., Bidwell, C.A. :
Genes contributing to genetic variation of muscling in sheep. Front Genet 3:164, 2012. Pubmed reference: 22952470. DOI: 10.3389/fgene.2012.00164.
2011 Boman, I.A., Klemetsdal, G., Nafstad, O., Blichfeldt, T., Våge, D.I. :
Selection based on progeny testing induces rapid changes in myostatin allele frequencies - a case study in sheep. J Anim Breed Genet 128:52-5, 2011. Pubmed reference: 21214644. DOI: 10.1111/j.1439-0388.2010.00879.x.
Sjakste, T., Paramonova, N., Grislis, Z., Trapina, I., Kairisa, D. :
Analysis of the single-nucleotide polymorphism in the 5'UTR and part of intron I of the sheep MSTN gene. DNA Cell Biol 30:433-44, 2011. Pubmed reference: 21323579. DOI: 10.1089/dna.2010.1153.
2010 Bignell, C.W., Malau-Aduli, A.E., Nichols, P.D., McCulloch, R., Kijas, J.W. :
East Friesian sheep carry a Myostatin allele known to cause muscle hypertrophy in other breeds. Anim Genet 41:445-6, 2010. Pubmed reference: 20219067. DOI: 10.1111/j.1365-2052.2010.02021.x.
Boman, I.A., Klemetsdal, G., Nafstad, O., Blichfeldt, T., Våge, D.I. :
Impact of two myostatin (MSTN) mutations on weight gain and lamb carcass classification in Norwegian White Sheep (Ovis aries). Genet Sel Evol 42:4, 2010. Pubmed reference: 20113462. DOI: 10.1186/1297-9686-42-4.
Braunschweig, M.H. :
Mutations in the bovine ABCG2 and the ovine MSTN gene added to the few quantitative trait nucleotides identified in farm animals: a mini-review. J Appl Genet 51:289-97, 2010. Pubmed reference: 20720303. DOI: 10.1007/BF03208858.
Hickford, J.G., Forrest, R.H., Zhou, H., Fang, Q., Han, J., Frampton, C.M., Horrell, A.L. :
Polymorphisms in the ovine myostatin gene (MSTN) and their association with growth and carcass traits in New Zealand Romney sheep. Anim Genet 41:64-72, 2010. Pubmed reference: 19799595. DOI: 10.1111/j.1365-2052.2009.01965.x.
Takeda, H., Charlier, C., Farnir, F., Georges, M. :
Demonstrating polymorphic miRNA-mediated gene regulation in vivo: application to the g+6223G->A mutation of Texel sheep. RNA 16:1854-63, 2010. Pubmed reference: 20679369. DOI: 10.1261/rna.2131110.
2009 Boman, I.A., Våge, D.I. :
An insertion in the coding region of the myostatin (MSTN) gene affects carcass conformation and fatness in the Norwegian Spaelsau (Ovis aries). BMC Res Notes 2:98, 2009. Pubmed reference: 19505313. DOI: 10.1186/1756-0500-2-98.
Boman, I.A., Klemetsdal, G., Blichfeldt, T., Nafstad, O., Våge, D.I. :
A frameshift mutation in the coding region of the myostatin gene (MSTN) affects carcass conformation and fatness in Norwegian White Sheep (Ovis aries). Anim Genet 40:418-22, 2009. Pubmed reference: 19392824. DOI: 10.1111/j.1365-2052.2009.01855.x.
Gong, Y.F., Li, X.L., Liu, Z.Z., Jin, X.M., Zhou, R.Y., Li, L.H., Zhang, Q. :
SNP detection and haplotype analysis in partial sequence of MSTN gene in sheep. Genetika 45:1646-9, 2009. Pubmed reference: 20198976.
Hickford, J.G., Forrest, R.H., Zhou, H. :
Association between a g.+6723G-A SNP in the myostatin gene (MSTN) and carcass traits in New Zealand Texel sheep. J Anim Sci 87:1853, 2009. Pubmed reference: 19443859. DOI: 10.2527/jas.2009-1960.
Johnson, P.L., Dodds, K.G., Bain, W.E., Greer, G.J., McLean, N.J., McLaren, R.J., Galloway, S.M., van Stijn, T.C., McEwan, J.C. :
Investigations into the GDF8 g+6723G-A polymorphism in New Zealand Texel sheep. J Anim Sci 87:1856-64, 2009. Pubmed reference: 19251921. DOI: 10.2527/jas.2008-1508.
2008 Hadjipavlou, G., Matika, O., Clop, A., Bishop, S.C. :
Two single nucleotide polymorphisms in the myostatin (GDF8) gene have significant association with muscle depth of commercial Charollais sheep. Anim Genet 39:346-53, 2008. Pubmed reference: 18462481. DOI: 10.1111/j.1365-2052.2008.01734.x.
Meng, X.R., Guo, J., Zhao, Q.J., Ma, Y.H., Guan, W.J., Liu, D., Di, R., Qiao, H.Y., Na, R.S. :
[Variation of MSTN gene UTR in eleven sheep breeds]. Yi Chuan 30:1585-90, 2008. Pubmed reference: 19073574. DOI: 10.3724/sp.j.1005.2008.01585.
Rodgers, B.D., Garikipati, D.K. :
Clinical, agricultural, and evolutionary biology of myostatin: a comparative review. Endocr Rev 29:513-34, 2008. Pubmed reference: 18591260. DOI: 10.1210/er.2008-0003.
Zhou, H., Hickford, J.G., Fang, Q. :
Variation in the coding region of the myostatin (GDF8) gene in sheep. Mol Cell Probes 22:67-8, 2008. Pubmed reference: 17935943. DOI: 10.1016/j.mcp.2007.08.004.
2007 Du, R., An, X.R., Chen, Y.F., Qin, J. :
Some motifs were important for myostatin transcriptional regulation in sheep (Ovis aries). J Biochem Mol Biol 40:547-53, 2007. Pubmed reference: 17669271. DOI: 10.5483/bmbrep.2007.40.4.547.
Du, R., An, X., Chen, Y., Qin, J. :
Functional analysis of the Myostatin gene promoter in sheep. Sci China C Life Sci 50:648-54, 2007. Pubmed reference: 17879064. DOI: 10.1007/s11427-007-0085-2.
Kijas, JW., Mcculloch, R., Hocking Edwards, JE., Oddy, VH., Lee, SH., van der Werf, J. :
Evidence for multiple alleles effecting muscling and fatness at the Ovine GDF8 locus. BMC Genet 8:80, 2007. Pubmed reference: 17996073. DOI: 10.1186/1471-2156-8-80.
Zhang, L., Yang, X., An, X., Chen, Y. :
Myostatin gene targeting in cultured China Han ovine myoblast cells. Animal 1:1401-8, 2007. Pubmed reference: 22444913. DOI: 10.1017/S1751731107000717.
2006 Clop, A., Marcq, F., Takeda, H., Pirottin, D., Tordoir, X., Bibe, B., Bouix, J., Caiment, F., Elsen, JM., Eychenne, F., Larzul, C., Laville, E., Meish, F., Milenkovic, D., Tobin, J., Charlier, C., Georges, M. :
A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nat Genet 38:813-818, 2006. Pubmed reference: 16751773. DOI: 10.1038/ng1810.
Georges, M., Clop, A., Marcq, F., Takeda, H., Pirottin, D., Hiard, S., Tordoir, X., Caiment, F., Meish, F., Bibé, B., Bouix, J., Elsen, J.M., Eychenne, F., Laville, E., Larzul, C., Milenkovic, D., Tobin, J., Charlier, A.C. :
Polymorphic microRNA-target interactions: a novel source of phenotypic variation. Cold Spring Harb Symp Quant Biol 71:343-50, 2006. Pubmed reference: 17381315. DOI: 10.1101/sqb.2006.71.056.
2005 Du, R., Chen, YF., An, XR., Yang, XY., Ma, Y., Zhang, L., Yuan, XL., Chen, LM., Qin, J. :
Cloning and sequence analysis of myostatin promoter in sheep. DNA Seq 16:412-7, 2005. Pubmed reference: 16287620. DOI: 10.1080/10425170500226474.
Johnson, PL., McEwan, JC., Dodds, KG., Purchas, RW., Blair, HT. :
Meat quality traits were unaffected by a quantitative trait locus affecting leg composition traits in Texel sheep. J Anim Sci 83:2729-35, 2005. Pubmed reference: 16282610. DOI: 10.2527/2005.83122729x.
Johnson, PL., McEwan, JC., Dodds, KG., Purchas, RW., Blair, HT. :
A directed search in the region of GDF8 for quantitative trait loci affecting carcass traits in Texel sheep. J Anim Sci 83:1988-2000, 2005. Pubmed reference: 16100053. DOI: 10.2527/2005.8391988x.
2004 Laville, E., Bouix, J., Sayd, T., Bibe, B., Elsen, JM., Larzul, C., Eychenne, F., Marcq, F., Georges, M. :
Effects of a quantitative trait locus for muscle hypertrophy from Belgian Texel sheep on carcass conformation and muscularity. J Anim Sci 82:3128-37, 2004. Pubmed reference: 15542458.

Edit History

  • Created by Imke Tammen2 on 20 Jan 2023
  • Changed by Imke Tammen2 on 20 Jan 2023
  • Changed by Imke Tammen2 on 25 Mar 2023
  • Changed by Imke Tammen2 on 12 Dec 2023