OMIA 000683-9913 : Muscular hypertrophy (double muscling) in Bos taurus

In other species: chicken , dog , pig

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1997

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 name: Double muscling

Species-specific description: The double-muscle trait in cattle is characterised by an increase in muscle mass of approx 20%, resulting in substantially higher meat yield, a higher proportion of expensive cuts of meat, and lean and very tender meat, for which a substantial premium is paid. The trait is autosomal recessive, and the locus has been given the symbol mh. It occurs at such a high frequency in Piedmontese and Belgian Blue cattle that it is characteristic of these breeds. However, it also occurs in other breeds. Along with its obvious advantages, double-muscling also has one major drawback - a greatly increased incidence of calving difficulties, to the extent that Caesarian sections are the rule for deliveries within these breeds. However, its advantages are sufficient that double-muscled cattle play a major role in animal agriculture in several countries, and are found in many countries.

In addition to naturally occurring variants for this trait, variants have been created artificially: Genetically-modifed organism; GMO.

History: The double-muscle trait in cattle was first described by Culley (1807).

Mapping: A genome scan using 213 mapped microsatellite markers in a Belgian Blue X Friesian backcross, conducted by Charlier et al. (1995), showed that the mh locus is at the centromeric end of chromosome 2, approximately 3.1 cM from microsatellite TCLA44. In mid 1997, McPherron et al. (1997) published the results of investigations into the gene for myostatin, a member of the transforming-growth-factor-beta-1 superfamily of peptides: mice in which the myostatin gene had been "knocked out" have a phenotype very similar to double-muscling. This immediately suggested a "candidate" gene for mh. Before long, both physical and linkage mapping had shown that myostatin maps to the mh region of bovine chromosome 2 (Grobet et al., 1997; Smith et al., 1997), making it a very likely candidate for the mh gene.

Molecular basis: Sequencing of myostatin DNA from homozygous normals and double-muscled cattle revealed an 11-bp deletion (of nucleotides 821 to 831), resulting in a frameshift and subsequent premature termination, in the bioactive carboxy-terminal domain of the gene in Belgian Blue cattle (Grobet et al., 1997; Kambadur et al., 1997; McPherron and Lee, 1997). This is a region that is very highly conserved in the TGF family of peptides. The same mutation is responsible for double-muscling in the Asturiana breed (Grobet et al. 1998; Georges et al., 1998).

In contrast, double-muscled Piedmontese cattle have a G-A transition that changes a cysteine residue to a tyrosine in the same highly-conserved region of the gene (Kambadur et al., 1997; McPherron and Lee, 1997).

In a screen of 35 double-muscled cattle from 10 European breeds, seven different sequence variants (alleles) were discovered in the coding region of the myostatin gene (Grobet et al., 1998; Georges et al., 1998). Five of these could cause a deficiency of myostatin: the 11bp deletion already described; an insertion/deletion in which 10 unrelated bases are inserted in the place a 7 bases that have been deleted at nucleotide 418; a C-T transition at nucleotide 610; a G-T transversion at nucleotide 676; and a G-A transition at nucleotide 938. Two other mutants were unlikely to cause a deficiency: a C-A transversion at nucleotide 282 (resulting in a conservative Phe-Leu amino-acid substitution); and a silent C-T transition at nucleotide 414. For most of the breeds, double-muscled animals were homozygous for one of the five harmful mutations, or were compound heterozygotes for two mutants. Obviously, there is considerable genetical heterogeneity in the cause of double muscling. Furthermore, the mutations are not all unique to one breed: two are shared by more than one breed. In addition, two breeds (Limousin and Blond d'Aquitane) have double-muscling but do not have any of the five harmful mutations. Clearly, there are more harmful mutations to be discovered. More importantly, the discovery that mutations in the myostatin gene have a profound effect on meat yield and quality opens the way for elucidating the role of myostatin in meat production, which in turn will suggest novel (possibly non-genetic) ways of enhancing meat yield and quality.

Dierks et al. (2015) reported a novel MSTN mutation (c.191T>C, p.Leu64Pro) in double-muscled German Gelbvieh cattle.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MSTN myostatin Bos taurus 2 NC_037329.1 (6278864..6285491) MSTN Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Maine Anjou Muscular hypertrophy (double muscling) MSTN D182N missense p.D182N 2002 Reference not in PubMed; see OMIA 000683-9913 for reference details
Angus Limousin Muscular hypertrophy (double muscling) MSTN missense UMD 3.1 2 g.6213980A>C c.282C>A p.Phe94Leu rs110065568 1998 9501304 Breed and variant information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)
Blonde d'Aquitaine Charolais Limousin Muscular hypertrophy (double muscling) MSTN nonsense (stop-gain) UMD 3.1 2 g.6216138C>T c.610C>T p.Q204* rs110344317 1998 9501304 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool
Maine Anjou Marchigiana Muscular hypertrophy (double muscling) MSTN nonsense (stop-gain) UMD 3.1 2 g.6216204G>T c.676G>T p.E226* 1998 9501304 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool; Breed information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)
Maine Anjou Marchigiana Muscular hypertrophy (double muscling) MSTN nonsense (stop-gain) UMD 3.1 2 g.6218432G>T c.1004G>T p.E291* 2013 22497537 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool; Breed information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)
Gelbvieh Muscular hypertrophy (double muscling) MSTN missense UMD3.1 2 g.6213889T>C c.191T>C p.L64P rs449270213 2015 25515003 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool
Parthenaise Muscular hypertrophy (double muscling) MSTN missense UMD3.1 2 g.6214012C>G c.314C>G p.Ser105Cys 2002 Reference not in PubMed; see OMIA 000683-9913 for reference details Breed and variant information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)
Maine Anjou Muscular hypertrophy (double muscling) MSTN nt419(del7-ins10) indel, small (<=20) UMD3.1 2 g.6215947 c.419_425del7, c418_426ins10 an insertion/deletion in which 10 unrelated bases are inserted in the place a 7 bases that have been deleted at nucleotide 418 1998 9501304 Variant information kindly provided or confirmed by Hubert Pausch, including information from Additional Table 6 of Jansen et al. (2013) BMC Genomics201314:446 https://doi.org/10.1186/1471-2164-14-446
Angus Asturiana Belgian Blue Blonde d'Aquitaine Braford Limousin Murray Grey Parthenaise Santa Gertrudis South Devon Muscular hypertrophy (double muscling) MSTN deletion, small (<=20) UMD3.1 2 g.6218379delATGAACACTCC c.821-831delTGAACACTCCA p.Glu275ArgfsX14 1997 9288100 Breed and variant information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)
Gasconne Parthenaise Piedmontese Muscular hypertrophy (double muscling) MSTN missense UMD3.1 2 g.6218499G>A c.938G>A p.C313Y 1997 9314496 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool; Breed information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)

References


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.
2018 Aiello, D., Patel, K., Lasagna, E. :
The myostatin gene: an overview of mechanisms of action and its relevance to livestock animals. Anim Genet :, 2018. Pubmed reference: 30125951. DOI: 10.1111/age.12696.
2016 Leroy, G., Besbes, B., Boettcher, P., Hoffmann, I., Capitan, A., Baumung, R. :
Rare phenotypes in domestic animals: unique resources for multiple applications. Anim Genet 47:141-53, 2016. Pubmed reference: 26662214. DOI: 10.1111/age.12393.
Randhawa, I.A., Khatkar, M.S., Thomson, P.C., Raadsma, H.W. :
A Meta-Assembly of Selection Signatures in Cattle. PLoS One 11:e0153013, 2016. Pubmed reference: 27045296. DOI: 10.1371/journal.pone.0153013.
2015 Dierks, C., Eder, J., Glatzer, S., Lehner, S., Distl, O. :
A novel myostatin mutation in double-muscled German Gelbvieh. Anim Genet 46:91-2, 2015. Pubmed reference: 25515003. DOI: 10.1111/age.12242.
Zhao, L.H., Zhao, Y.H., Liang, H., Yun, T., Han, X.J., Zhang, M.L., Zhou, X., Hou, D.X., Li, R.F., Li, X.L. :
A promoter trap vector for knocking out bovine myostatin gene with high targeting efficiency. Genet Mol Res 14:2750-61, 2015. Pubmed reference: 25867424. DOI: 10.4238/2015.March.31.5.
2014 Druet, T., Ahariz, N., Cambisano, N., Tamma, N., Michaux, C., Coppieters, W., Charlier, C., Georges, M. :
Selection in action: dissecting the molecular underpinnings of the increasing muscle mass of Belgian blue cattle. BMC Genomics 15:796, 2014. Pubmed reference: 25228463. DOI: 10.1186/1471-2164-15-796.
Luo, J., Song, Z., Yu, S., Cui, D., Wang, B., Ding, F., Li, S., Dai, Y., Li, N. :
Efficient generation of myostatin (MSTN) biallelic mutations in cattle using zinc finger nucleases. PLoS One 9:e95225, 2014. Pubmed reference: 24743319. DOI: 10.1371/journal.pone.0095225.
Yang, C., Tong, H., Ma, X., Du, W., Liu, D., Yang, Y., Yan, Y. :
Myostatin knockout in bovine fetal fibroblasts by using TALEN. Yi Chuan 36:685-90, 2014. Pubmed reference: 25076033. DOI: 10.3724/SP.J.1005.2014.0685.
2013 Druet, T., Pérez-Pardal, L., Charlier, C., Gautier, M. :
Identification of large selective sweeps associated with major genes in cattle. Anim Genet 44:758-62, 2013. Pubmed reference: 23859468. DOI: 10.1111/age.12073.
Howard, J.T., Kachman, S.D., Nielsen, M.K., Mader, T.L., Spangler, M.L. :
The effect of myostatin genotype on body temperature during extreme temperature events. J Anim Sci 91:3051-8, 2013. Pubmed reference: 23572263. DOI: 10.2527/jas.2012-6180.
Miretti, S., Martignani, E., Accornero, P., Baratta, M. :
Functional effect of mir-27b on myostatin expression: a relationship in Piedmontese cattle with double-muscled phenotype. BMC Genomics 14:194, 2013. Pubmed reference: 23510267. DOI: 10.1186/1471-2164-14-194.
O'Rourke, B.A., Greenwood, P.L., Arthur, P.F., Goddard, M.E. :
Inferring the recent ancestry of myostatin alleles affecting muscle mass in cattle. Anim Genet 44:86-90, 2013. Pubmed reference: 22497537. DOI: 10.1111/j.1365-2052.2012.02354.x.
2012 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 Stinckens, A., Georges, M., Buys, N. :
Mutations in the myostatin gene leading to hypermuscularity in mammals: indications for a similar mechanism in fish? Anim Genet 42:229-34, 2011. Pubmed reference: 21175702. DOI: 10.1111/j.1365-2052.2010.02144.x.
2010 Warner, RD., Greenwood, PL., Pethick, DW., Ferguson, DM. :
Genetic and environmental effects on meat quality. Meat Sci 86:171-83, 2010. Pubmed reference: 20561754. DOI: 10.1016/j.meatsci.2010.04.042.
2009 Hudson, NJ., Reverter, A., Dalrymple, BP. :
A differential wiring analysis of expression data correctly identifies the gene containing the causal mutation. PLoS Comput Biol 5:e1000382, 2009. Pubmed reference: 19412532. DOI: 10.1371/journal.pcbi.1000382.
2008 Esmailizadeh, A.K., Bottema, C.D., Sellick, G.S., Verbyla, A.P., Morris, C.A., Cullen, N.G., Pitchford, W.S. :
Effects of the myostatin F94L substitution on beef traits. J Anim Sci 86:1038-46, 2008. Pubmed reference: 18245504. DOI: 10.2527/jas.2007-0589.
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.
2007 Sellick, G.S., Pitchford, W.S., Morris, C.A., Cullen, N.G., Crawford, A.M., Raadsma, H.W., Bottema, C.D. :
Effect of myostatin F94L on carcass yield in cattle. Anim Genet 38:440-6, 2007. Pubmed reference: 17617213. DOI: 10.1111/j.1365-2052.2007.01623.x.
2006 Best, LG., Gilbert-Barness, E., Gerrard, DE., Gendron-Fitzpatrick, A., Opitz, JM. :
"Double-muscle" trait in cattle: a possible model for Wiedemann-Beckwith syndrome. Fetal Pediatr Pathol 25:9-20, 2006. Pubmed reference: 16754485. DOI: 10.1080/15227950600701503.
De la Rosa-Reyna, XF., Rodriguez Perez, MA., Sifuentes-Rincon, AM. :
Microsatellite polymorphism in intron 1 of the bovine myostatin gene. J Appl Genet 47:55-7, 2006. Pubmed reference: 16424609.
Dominique, JE., Gerard C. :
Myostatin regulation of muscle development: molecular basis, natural mutations, physiopathological aspects. Exp Cell Res 312:2401-14, 2006. Pubmed reference: 16793037. DOI: 10.1016/j.yexcr.2006.04.012.
Forbes, D., Jackman, M., Bishop, A., Thomas, M., Kambadur, R., Sharma, M. :
Myostatin auto-regulates its expression by feedback loop through Smad7 dependent mechanism. J Cell Physiol 206:264-72, 2006. Pubmed reference: 16110474. DOI: 10.1002/jcp.20477.
2005 Bellinge, RH., Liberles, DA., Iaschi, SP., O'brien, PA., Tay, GK. :
Myostatin and its implications on animal breeding: a review. Anim Genet 36:1-6, 2005. Pubmed reference: 15670124. DOI: 10.1111/j.1365-2052.2004.01229.x.
Biagini, D., Lazzaroni, C. :
Carcass dissection and commercial meat yield in Piemontese and Belgian Blue double-muscled young bulls Livestock Production Science 98:199-204, 2005.
Bouley, J., Meunier, B., Chambon, C., De Smet, S., Hocquette, JF., Picard, B. :
Proteomic analysis of bovine skeletal muscle hypertrophy. Proteomics 5:490-500, 2005. Pubmed reference: 15627970. DOI: 10.1002/pmic.200400925.
Di Stasio, L., Rolando, A. :
A PCR-RFLP method for genotyping the myostatin locus in Piemontese cattle. Anim Genet 36:521, 2005. Pubmed reference: 16293132. DOI: 10.1111/j.1365-2052.2005.01356.x.
Listrat, A., Hocquette, JF., Picard, B., Menissier, F., Djiane, J., Jammes, H. :
Growth hormone receptor gene expression in the skeletal muscle of normal and double-muscled bovines during foetal development. Reprod Nutr Dev 45:393-403, 2005. Pubmed reference: 16045888. DOI: 10.1051/rnd:2005036.
2004 Fernandez, C., Barroso, A., Cañón, J., Dunner, S. :
Myostatin dominant negative allele products interact positively with wild type monomers. Anim Biotechnol 15:133-43, 2004. Pubmed reference: 15595699. DOI: 10.1081/LABT-200035054.
Martyn, JK., Bass, JJ., Oldham, JM. :
Skeletal muscle development in normal and double-muscled cattle. Anat Rec A Discov Mol Cell Evol Biol 281:1363-71, 2004. Pubmed reference: 15532043. DOI: 10.1002/ar.a.20140.
Valkeners, D., Théwis, A., Piron, F., Beckers, Y. :
Effect of imbalance between energy and nitrogen supplies on microbial protein synthesis and nitrogen metabolism in growing double-muscled Belgian Blue bulls. J Anim Sci 82:1818-25, 2004. Pubmed reference: 15217010.
2003 Dunner, S., Miranda, M.E., Amigues, Y., Cañón, J., Georges, M., Hanset, R., Williams, J., Ménissier, F. :
Haplotype diversity of the myostatin gene among beef cattle breeds. Genet Sel Evol 35:103-18, 2003. Pubmed reference: 12605853. DOI: 10.1051/gse:2002038.
Fiems, L.O., De Campeneere, S., Van Caelenbergh, W., De Boever, J.L., Vanacker, J.M. :
Carcass and meat quality in double-muscled Belgian Blue bulls and cows Meat Science 63:345-352, 2003.
Marchitelli, C., Savarese, M.C., Crisà, A., Nardone, A., Marsan, P.A., Valentini, A. :
Double muscling in Marchigiana beef breed is caused by a stop codon in the third exon of myostatin gene. Mamm Genome 14:392-5, 2003. Pubmed reference: 12879361. DOI: 10.1007/s00335-002-2176-5.
2002 Berry, C., Thomas, M., Langley, B., Sharma, M., Kambadur, R. :
Single cysteine to tyrosine transition inactivates the growth inhibitory function of Piedmontese myostatin American Journal of Physiology - Cell Physiology 283:C135-C141, 2002. Pubmed reference: 12055081. DOI: 10.1152/ajpcell.00458.2001.
Froidmont, E., Beckers, Y., Thewis, A. :
Determination of the methionine requirement of finishing double-muscled Belgian blue bulls with a three-step method Canadian Journal of Animal Science 82:95-102, 2002.
Froidmont, E., Rondia, P., Thewis, A., Beckers, Y. :
Rumen escape of methionine and lysine administered intraruminally to growing double-muscled Belgian Blue bulls Reproduction, Nutrition, Development 42:537-44, 2002. Pubmed reference: 12625418.
Goyache, F., Royo, L.J., Alvarez, I., Gutierrez, J.P. :
Testing a continuous variation in preweaning expression of muscular hypertrophy in beef cattle using field data Archiv fur Tierzucht-Archives of Animal Breeding 45:139-149, 2002.
Miranda, M.E., Amigues, Y., Boscher, M.Y., Menissier, F., Cortes, O., Dunner, S. :
Simultaneous genotyping to detect myostatin gene polymorphism in beef cattle breeds Journal of Animal Breeding & Genetics 119:361-366, 2002.
Ngapo, T.M., Berge, P., Culioli, J., De, Smet, S. :
Perimysial collagen crosslinking in Belgian Blue double-muscled cattle Food Chemistry 77:15-26, 2002.
Short, R.E., MacNeil, M.D., Grosz, M.D., Gerrard, D.E., Grings, E.E. :
Pleiotropic effects in Hereford, Limousin, and Piedmontese F-2 crossbred calves of genes controlling muscularity including the Piedmontese myostatin allele Journal of Animal Science 80:1-11, 2002. Pubmed reference: 11831504.
Webster, A.J.F. :
Rendering unto Caesar: Welfare problems in Belgian Blue cattle Veterinary Journal 163:228-229, 2002.
Wiener, P., Smith, J.A., Lewis, A.M., Woolliams, J.A., Williams, J.L. :
Muscle-related traits in cattle: The role of the myostatin gene in the South Devon breed Genetics Selection Evolution 34:221-232, 2002.
2001 Casas, E., Stone, R.T., Keele, J.W., Shackelford, S.D., Kappes, S.M., Koohmaraie, M. :
A comprehensive search for quantitative trait loci affecting growth and carcass composition of cattle segregating alternative forms of the myostatin gene Journal of Animal Science 79:854-860, 2001. Pubmed reference: 11325189.
De, Campeneere, S., Fiems, L.O., Boucque, C.V. :
Energy and protein requirements of Belgian Blue double-muscled bulls Animal Feed Science & Technology 90:153-167, 2001.
De, Campeneere, S., Fiems, L.O., De, Paepe, M., Vanacker, J.M., Boucque, C.V. :
Compositional data on Belgian Blue double-muscled bulls Animal Research 50:43-55, 2001.
Fiems, L.O., de, Campeneere, S., van, Caelenbergh, W., Boucque, C.V. :
Relationship between dam and calf characteristics with regard to dystocia in Belgian Blue double-muscled cows Animal Science 72:389-394, 2001.
Jeanplong, F., Sharma, M., Somers, W.G., Bass, J.J., Kambadur, R. :
Genomic organization and neonatal expression of the bovine myostatin gene Molecular & Cellular Biochemistry 220:31-37, 2001.
Keele, J.W., Fahrenkrug, S.C. :
Optimum mating systems for the myostatin locus in cattle Journal of Animal Science 79:2016-2022, 2001. Pubmed reference: 11518210.
Mozersky, S.M., Iandola, S.K., Marmer, W.N. :
Leather made from the hides of double-muscled cattle has satisfactory physical characteristics Journal of the American Leather Chemists Association 96:393-397, 2001.
Oldham, J.M., Martyn, J.A.K., Sharma, M., Jeanplong, F., Kambadur, R., Bass, J.J. :
Molecular expression of myostatin and MyoD is greater in double-muscled than normal-muscled cattle fetuses American Journal of Physiology - Regulatory Integrative & Comparative Physiology 280:R1488-R1493, 2001.
Raes, K., de, Smet, S., Demeyer, D. :
Effect of double-muscling in Belgian Blue young bulls on the intramuscular fatty acid composition with emphasis on conjugated linoleic acid and polyunsaturated fatty acids Animal Science 73:253-260, 2001.
Vandenheede, M., Nicks, B., Desiron, A., Canart, B. :
Mother-young relationships in Belgian Blue cattle after a Caesarean section: characterisation and effects of parity Applied Animal Behaviour Science 72:281-292, 2001. Pubmed reference: 11311422.
Wheeler, T.L., Shackleford, S.D., Casas, E., Cundiff, L.V., Koohmaraie, M. :
The effects of Piedmontese inheritance and myostatin genotype on the palatability of longissimus thoracis, gluteus medius, semimembranosus, and biceps femoris Journal of Animal Science 79:3069-3074, 2001. Pubmed reference: 11811461.
2000 Cambier, C., Clerbaux, T., Detry, B., Beerens, D., Frans, A., Gustin, P. :
Blood oxygen binding in double-muscled calves and dairy calves with conventional muscle conformation American Journal of Veterinary Research 61:299-304, 2000. Pubmed reference: 10714522.
Casas, E., Shackleford, S.D., Keele, J.W., Stone, R.T., Kappes, S.M., Koohmaraie, M. :
Quantitative trait loci affecting growth and carcass composition of cattle segregating alternate forms of myostatin Journal of Animal Science 78:560-569, 2000. Pubmed reference: 10764062.
De, Smet, S., Webb, E.C., Claeys, E., Uytterhaegen, L., Demeyer, D.I. :
Effect of dietary energy and protein levels on fatty acid composition of intramuscular fat in double-muscled Belgian Blue bulls Meat Science 56:73-79, 2000.
Froidmont, E., Beckers, Y., Thewis, A. :
Determination of the methionine requirement of growing double-muscled Belgian Blue bulls with a three-step method Journal of Animal Science 78:233-241, 2000. Pubmed reference: 10682826.
Karim, L., Coppieters, W., Grobet, L., Valentini, A., Georges, M. :
Convenient genotyping of six myostatin mutations causing double-muscling in cattle using a multiplex oligonucleotide ligation assay. Anim Genet 31:396-9, 2000. Pubmed reference: 11167526.
Smith, J.A., Lewis, A.M., Wiener, P., Williams, J.L. :
Genetic variation in the bovine myostatin gene in UK beef cattle: Allele frequencies and haplotype analysis in the South Devon Animal Genetics 31:306-309, 2000. Pubmed reference: 11105210.
1999 Antoniou, E., Grosz, M. :
PCR based detection of bovine myostatin Q204X mutation Animal Genetics 30:231-232, 1999. Pubmed reference: 10442997.
De, Campeneere, S., Fiems, L.O., Van, de, Voorde, G., Vanacker, J.M., Boucque, C.V., Demeyer, D.I. :
Estimation of chemical carcass composition from 8th rib characteristics with Belgian blue double-muscled bulls Meat Science 51:27-33, 1999.
Fahrenkrug, S.C., Casas, E., Keele, J.W., Smith, T.P.L. :
Technical note: Direct genotyping of the double-muscling locus (mh) in piedmontese and Belgian Blue cattle by fluorescent PCR Journal of Animal Science 77:2028-2030, 1999. Pubmed reference: 10461977.
Gariepy, C., Seoane, J.R., Cloteau, C., Martin, J.F., Roy, G.L. :
The use of double-muscled cattle breeds in terminal crosses: Meat quality Canadian Journal of Animal Science 79:301-308, 1999.
Hornick, J.L., van, Eenaeme, C., Clinquart, A., Gerard, O., Istasse, L. :
Different modes of food restriction and compensatory growth in double-muscled Belgian Blue bulls: animal performance, carcass and meat characteristics Animal Science 69:563-572, 1999.
Lammoglia, M.A., Bellows, R.A., Grings, E.E., Bergman, J.W. :
Effects of prepartum supplementary fat and muscle hypertrophy genotype on cold tolerance in newborn calves Journal of Animal Science 77:2227-2233, 1999. Pubmed reference: 10462003.
Listrat, A., Belair, L., Picard, B., Boulle, N., Geay, Y., Djiane, J., Jammes, H. :
Insulin-like growth factor II (IGF-II) mRNA expression during skeletal muscle development of double-muscled and normal bovine foetuses Reproduction, Nutrition, Development 39:113-124, 1999. Pubmed reference: 10222502.
Listrat, A., Picard, B., Geay, Y. :
Age-related changes and location of type I, III, IV, V and VI collagens during development of four foetal skeletal muscles of double-muscled and normal bovine animals Tissue & Cell 31:17-27, 1999. Pubmed reference: 10368982. DOI: 10.1054/tice.1998.0015.
Pirottin, D., Poncelet, D., Grobet, L., Royo, L.J., Brouwers, B., Masabanda, J., Takeda, H., Fries, R., Sugimoto, Y., Womack, J.E., Dunner, S., Georges, M. :
High-resolution, human-bovine comparative mapping based on a closed YAC contig spanning the bovine mh locus Mammalian Genome 10:289-293, 1999. Pubmed reference: 10051326.
Seoane, J.R., Lapierre, H., Roy, R.L. :
The use of double-muscled cattle breeds in terminal crosses: Animal performance and blood metabolites Canadian Journal of Animal Science 79:293-299, 1999.
de, Campeneere, S., Fiems, L.O., Vanacker, J.M., Boucque, C.V. :
Empty body chemical composition estimated from non-carcass parts in Belgian Blue double-muscled bulls Animal Science 68:223-229, 1999.
1998 Casas, E., Keele, J.W., Shackelford, S.D., Koohmaraie, M., Sonstegard, T.S., Smith, T.P.L., Kappes, S.M., Stone, R.T. :
Association of the muscle hypertrophy locus with carcass traits in beef cattle Journal of Animal Science 76:468-473, 1998. Pubmed reference: 9498354.
Georges, M., Grobet, L., Poncelet, D., Royo, L.J., Pirottin, D., Brouwers, B. :
Positional candidate cloning of the bovine MH locus identifies an allelic seris of mutations disrupting the myostatin function and causing double-muscling in cattle Proceedings of the 6th World Congress on Genetics Applied to Livestock Production 26:195-204, 1998.
Grobet, L., Poncelet, D., Royo, L.J., Brouwers, B., Pirottin, D., Michaux, C., Menissier, F., Zanotti, M., Dunner, S., Georges, M. :
Molecular definition of an allelic series of mutations disrupting the myostatin function and causing double-muscling in cattle Mammalian Genome 9:210-213, 1998. Pubmed reference: 9501304.
Listrat, A., Picard, B., Geay, Y. :
Age-related changes and location of type I, III and IV collagens during skeletal muscle development of double-muscled and normal bovine foetuses Journal of Muscle Research & Cell Motility 19:1-14, 1998.
Webb, E.C., Desmet, S., Vannevel, C., Martens, B., Demeyer, D.I. :
Effect of anatomical location on the composition of fatty acids in double-muscled Belgian Blue cows Meat Science 50:45-53, 1998.
1997 Anon. :
Muscle-bound cattle gene discovered Outlook on Agriculture 26:274, 1997.
Dickman, S. :
Agricultural genetics - gene mutation provides more meat on the hoof Science 277:1922-1923, 1997. Pubmed reference: 9333944.
Dickman, S. :
Agricultural genetics - gene mutation provides more meat on the hoof (vol 277, pg 1922, 1997) Science 278:2037, 1997.
Dunner, S., Charlier, C., Farnir, F., Brouwers, B., Canon, J., Georges, M. :
Towards interbreed IBD fine mapping of the MH locus - double-muscling in the Asturiana de los Valles breed involves the same locus as in the Belgian Blue cattle breed Mammalian Genome 8:430-435, 1997. Pubmed reference: 9166589.
Gagniere, H., Picard, B., Jurie, C., Geay, Y. :
Comparative study of metabolic differentiation of foetal muscle in normal and double-muscled cattle Meat Science 45:145-152, 1997.
Grobet, L., Martin, L.J.R., Poncelet, D., Pirottin, D., Brouwers, B., Riquet, J., Schoeberlein, A., Dunner, S., Menissier, F., Massabanda, J., Fries, R., Hanset, R., Georges, M. :
A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle Nature Genetics 17:71-74, 1997. Pubmed reference: 9288100. DOI: 10.1038/ng0997-71.
Hornick, J.L., Vaneenaeme, C., Diez, M., Minet, V., Istasse, L. :
Comparison of hindquarter metabolite uptakes in Belgian Blue double-muscled bulls at maintenance or during fattening Journal of Animal Science 75:3331-3341, 1997. Pubmed reference: 9420009.
Imschoot, J. :
Monitoring the pre-parturition period to determine the optimal time for caesarian section in double muscled cattle [Dutch] Vlaams Diergeneeskundig Tijdschrift 66:303-308, 1997.
Kambadur, R., Sharma, M., Smith, T.P.L., Bass, J.J. :
Mutations in myostatin (GDF8) in double-muscled Belgian Blue and Piedmontese cattle Genome Research 7:910-916, 1997. Pubmed reference: 9314496.
McPherron, A.C., Lawler, A.M., Lee, S-J. :
Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member Nature 387:83-90, 1997. Pubmed reference: 9139826. DOI: 10.1038/387083a0.
McPherron, A.C., Lee, S.J. :
Double muscling in cattle due to mutations in the myostatin gene Proceedings of the National Academy of Sciences of the United States of America 94:12457-12461, 1997. Pubmed reference: 9356471.
Rollin, F., Amory, H., Desmecht, D., Linden, A., Art, T., Lomba, F., Lekeux, P. :
Pulmonary function values in friesian and double-muscled calves during acute poikilocapnic hypoxia Zentralblatt Fur Veterinarmedizin - Reihe A 44:79-90, 1997. Pubmed reference: 9284633.
Smith, T.P.L., Lopezcorrales, N.L., Kappes, S.M., Sonstegard, T.S. :
Myostatin maps to the interval containing the bovine mh locus Mammalian Genome 8:742-744, 1997. Pubmed reference: 9321467.
Sonstegard, T.S., Lopezcorrales, N.L., Kappes, S.M., Beattie, C.W., Smith, T.P.L. :
Comparative mapping of human chromosome 2 identifies segments of conserved synteny near the bovine mh locus Mammalian Genome 8:751-755, 1997. Pubmed reference: 9321469.
Steen, D., Claeys, E., Uytterhaegen, L., Desmet, D., Demeyer, D. :
Early post-mortem conditions and the calpain/calpastatin system in relation to tenderness of double-muscled beef Meat Science 45:307-319, 1997.
Westhusin, M. :
From mighty mice to mighty cows Nature Genetics 17:4-5, 1997. Pubmed reference: 9288084. DOI: 10.1038/ng0997-4.
1995 Amory, H., Mcentee, K., Linden, A.S., Desmecht, D.J.M., Beduin, J.M.L., Dorio, V., Lekeux, P.M. :
Comparative assessment of right ventricular performance from the pressure-volume relationship in double-muscled and conventional calves Canadian Journal of Veterinary Research - Revue Canadienne de Recherche Veterinaire 59:135-141, 1995. Pubmed reference: 7648526.
Arthur, P.F. :
Double muscling in cattle - a review [Review] Australian Journal of Agricultural Research 46:1493-1515, 1995.
Charlier, C., Coppieters, W., Farnir, F., Grobet, L., Leroy, P.L., Michaux, C., Mni, M., Schwers, A., Vanmanshoven, P., Hanset, R., Georges, M. :
The MH gene causing double-muscling in cattle maps to bovine chromosome 2 Mammalian Genome 6:788-792, 1995. Pubmed reference: 8597635.
Clinquart, A., Vaneenaeme, C., Mayombo, A.P., Gauthier, S., Istasse, L. :
Plasma hormones and metabolites in cattle in relation to breed (Belgian Blue vs Holstein) and conformation (double- muscled vs dual-purpose type) Veterinary Research Communications 19:185-194, 1995. Pubmed reference: 7571392.
Picard, B., Gagniere, H., Robelin, J., Geay, Y. :
Comparison of the foetal development of muscle in normal and double-muscled cattle Journal of Muscle Research & Cell Motility 16:629-639, 1995.
Shahin, K.A. :
Sex differences in muscle topography and its relationship to muscularity in Double Muscled cattle Livestock Production Science 43:1-13, 1995.
1994 Amory, H., Desmecht, D.J.M., Linden, A.S., Mcentee, K., Rollin, F.A., Beduin, J.M.L., Genicot, B.C., Dorio, V., Lekeux, P.M. :
Comparison of Cardiac Function in Double-Muscled Calves and in Calves with Conventional Muscular Conformation American Journal of Veterinary Research 55:561-566, 1994. Pubmed reference: 8017704.
Genicot, B., Mouligneau, F., Close, R., Lekeux, P. :
Functional Effects of a Muscarinic Receptor Blockade During Acute Respiratory Distress Syndrome in Double-Muscled Calves Veterinary Record 134:110-113, 1994. Pubmed reference: 8171769.
Gerrard, D.E., Grant, A.L. :
Insulin-like growth factor-II expression in developing skeletal muscle of double muscled and normal cattle Domestic Animal Endocrinology 11:339-347, 1994. Pubmed reference: 7828428.
Lekeux, P., Amory, H., Desmecht, D., Gustin, P., Linden, A., Rollin, F. :
Oxygen Transport Chain in Double-Muscled Blue Belgian Cattle British Veterinary Journal 150:463-471, 1994. Pubmed reference: 7953580. DOI: 10.1016/S0007-1935(05)80197-6.
Uytterhaegen, L., Claeys, E., Demeyer, D., Lippens, M., Fiems, L.O., Boucque, C.Y., Vandevoorde, G., Bastiaens, A. :
Effects of Double-Muscling on Carcass Quality, Beef Tenderness and Myofibrillar Protein Degradation in Belgian Blue White Bulls Meat Science 38:255-267, 1994.
Vansoom, A., Mijten, P., Vanvlaenderen, I., Vandenbranden, J., Mahmoudzadeh, A.R., Dekruif, A. :
Birth of Double-Muscled Belgian Blue Calves After Transfer of in Vitro Produced Embryos into Dairy Cattle Theriogenology 41:855-867, 1994.
1993 Amory, H., Mcentee, K., Linden, A.S., Desmecht, D.J.M., Beduin, J.M.L., Dorio, V., Lekeux, P.M. :
Comparison of the Cardiac Pumping Capability and Cardiac Pumping Reserve in Double-Muscled and Conventional Calves Canadian Journal of Physiology and Pharmacology 71:946-951, 1993. Pubmed reference: 8180890.
Genicot, B., Mouligneau, F., Lindsey, J.K., Lambert, P., Close, R., Lekeux, P. :
Efficiency of 5-Hydroxytryptamine Receptor Blockade as Therapeutic Measure During Acute Respiratory Distress Syndrome in Double-Muscled Cattle Journal of Veterinary Medicine Series A - Zentralblatt Fur Veterinarmedizin Reihe A - Physiology Pathology Clinical Medicine 40:185-193, 1993.
Gerrard, D.E., Judge, M.D. :
Induction of Myoblast Proliferation in L6 Myoblast Cultures by Fetal Serum of Double-Muscled and Normal Cattle Journal of Animal Science 71:1464-1470, 1993. Pubmed reference: 8325806.
1992 Amory, H., Rollin, F., Desmecht, D., Linden, A., Lekeux, P. :
Cardiovascular Response to Acute Hypoxia in Double-Muscled Calves Research in Veterinary Science 52:316-324, 1992. Pubmed reference: 1620964.
Roets, E., Burvenich, C., Roberts, M. :
Muscarinic Receptor Subtypes, beta-Adrenoceptors and cAMP in the Tracheal Smooth Muscle of Conventional and Double-Muscled Calves Veterinary Research Communications 16:465-476, 1992. Pubmed reference: 1338239.
1991 Degeest, J., Sustronck, B., Muylle, E. :
Neonatal Dyspnoea in Double-Muscled Calves Vlaams Diergeneeskundig Tijdschrift 60:26-31, 1991.
Owen, J.B., Hanset, R., Axford, R.F.E. :
The Major Gene of Muscular Hypertrophy in the Belgian Blue Cattle Breed :467-478, 1991.
Shahin, K.A., Berg, R.T., Price, M.A. :
Muscle and Bone Distribution in Mature Normal and Double Muscled Cows Livestock Production Science 28:291-303, 1991.
1990 Arthur, P.F., Makarechian, M., Salmon, R.K., Price, M.A. :
Plasma Growth Hormone and Insulin Concentrations in Double- Muscled and Normal Bull Calves Journal of Animal Science 68:1609-1615, 1990. Pubmed reference: 2200773.
Ott, R.S. :
Muscular Hypertrophy in Beef Cattle - Deja-Vu Journal of the American Veterinary Medical Association 196:413-415, 1990. Pubmed reference: 2404931.
1989 Arthur, P.F., Makarechian, M., Price, M.A. :
Mating double-muscled and normal cattle for lean beef production Livestock Production Science 21:201-211, 1989.
Arthur, P.F., Makarechian, M., Price, M.A., Berg, R.T. :
Carcass Characteristics of Yearling Normal and Double Muscle Cross Bulls Canadian Journal of Animal Science 69:897-903, 1989.
Arthur, P.F., Makarechian, M., Price, M.A., Berg, R.T. :
Heterosis, maternal and direct effects in double-muscled and normal cattle: I. Reproduction and growth traits Journal of Animal Science 67:902-910, 1989. Pubmed reference: 2715117.
Arthur, P.F., Makarechian, M., Price, M.A., Berg, R.T. :
Heterosis, maternal and direct effects in double-muscled and normal cattle. II. Carcass traits of young bulls Journal of Animal Science 67:911-919, 1989. Pubmed reference: 2715118.
1988 Arthur, P.F., Makarechian, M., Price, M.A. :
Incidence of dystocia and perinatal mortality resulting from reciprocal crossing of double-muscled and normal cattle Canadian Veterinary Journal 29:163-167, 1988.
1987 Arthur, P.F., Makarechian, M., Price, M.A. :
Crossing double-muscled and normal cattle: reproductive performance Agriculture and Forestry Bulletin, University of Alberta :72-75, 1987.
Laurans, A. de, Lukaszewicz, M. :
Influence of the muscular hypertrophy gene on the skeleton and hypertrophy of individual muscles in cattle Animal Science Papers and Reports, Institute of Genetics and Animal Breeding Jastrzebiec, Polish Academy of Sciences :89-101, 1987.
1986 Hanset, R. :
Doubling muscling in cattle :71-80, 1986.
Shahin, K.A., Berg, R.T., Price, M.A. :
Sex differences in carcass composition and tissue distribution in mature double muscled cattle Canadian Journal of Animal Science 66:625-636, 1986.
1985 Hanset, R., Michaux, C. :
On the genetic determinism of muscular hypertrophy in the Belgian White and Blue cattle breed. II. Genetics, Selection, Evolution 17:369-386, 1985.
Hanset, R., Michaux, C. :
On the genetic determinism of muscular hypertrophy in the Belgian White and Blue cattle breed. I. Genetics, Selection, Evolution 17:359-368, 1985.
1981 Hanset, R. :
Double muscling in cattle : Its inheritance : Its meaning for beef production Annales de Medecine Veterinaire 125:85-95, 1981.
Michaux, C., Hanset, R. :
Sexual development of double-muscled and conventional bulls. I. Testicular growth Zeitschrift fur Tierzuchtung und Zuchtungsbiologie 98:29-37, 1981.
Michaux, C., Hanset, R. :
Sexual development of double-muscled and conventional bulls. II. Plasma testosterone and luteinizing hormone (LH) levels Zeitschrift fur Tierzuchtung und Zuchtungsbiologie 98:38-44, 1981.
Novakofski, J.E., Kauffman, R.G., Cassens, R.G. :
Biological detection of heterozygosity for double muscling in cattle. 1. Terminal innervation ratio Journal of Animal Science 52:1430-1436, 1981. Pubmed reference: 7298527.
1979 Hanset, R. :
Feed intake and feed efficiency in double-muscled and conventional cattle Zeitschrift fur Tierzuchtung und Zuchtungsbiologie 96:260-269, 1979.
1969 Oliver, W.M., Cartwright, T.C. :
Double muscling in cattle. A review of expression genetics and economic implications Texas Agricultural Experiment Station Technical Report :58, 1969.
1968 Kidwell, J.F., Vernon, E.H. :
Muscular hypertrophy in cattle Journal of Heredity 43:62-, 1968.
1967 Hanset, R. :
[The problem of muscular hypertrophy or the culard character in the Central and Upper Belgium breed] Annales de Medecine Veterinaire 111:140-180, 1967.
1966 Ansay, M., Gillet, A. :
[Study of some blood and urinary components in cattle with muscular hypertrophy. II. Creatine and creatinine] Annales de Medecine Veterinaire 110:512-541, 1966.
Ansay, M., Gillet, A. :
[Study of some constituents of blood and urine in muscular hypertrophy in cattle. I. Urea and amino acids] Annales de Medecine Veterinaire 110:274-302, 1966.
1964 Boccard, R. :
Relationship between muscular hypertrophy and collagen metabolism in 'double rump' cattle Annales de Zootechnie 13:389-391, 1964.
Lawrie, R.A., Pomeroy, R.W., Williams, D.R. :
Studies in the muscles of meat animals. IV. Comparative composition of muscles from 'doppelander' and normal sibling heifers Journal of Agricultural Science 62:89-92, 1964.
1963 Dejong, S. :
[Cattle with muscular hypertrophy] Veeteelt- en Zuivelberichten 6:174-178, 1963.
1962 Nuvy, A., Vissac, B. :
The 'curard' of double- muscled phenomenon in cattle Union Nationale des Livres Geneologiques :52, 1962.
Pomeroy, R.W., Williams, D.R. :
Muscular hypertrophy in cattle Animal Production 4:302 only, 1962.
1961 Hanset, R. :
The problem of muscular hypertrophy in the rump of cattle Annales de Medecine Veterinaire 105:14-31, 1961.
Raimondi, R. :
[Fattening and slaughter tests to compare normal and 'double-muscled' Piedmont calves] Annali della Sperimentazione Agraria 15:105-151, 1961.
1807 Culley, G. :
Observations on livestock, 4th ed. G. Woodfall, London, UK. :, 1807.

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