Myostatin (GDF8) acts as a negative regulator of muscle growth. Mutations in the gene are responsible for the double muscling phenotype in several European cattle breeds. Here we describe the sequence of the upstream 5′ region of the myostatin gene. The sequence analysis was carried out on three animals of nine European cattle breeds, with the aim to search for polymorphisms. A T/A polymorphism at –371 and a G/C polymorphism at –805 (relative to ATG) were found. PCR- RFLP was used to further screen 353 animals of the nine breeds studied and to assess the frequencies of the SNPs. The promoter region of the gene contains several binding sites for transcription factors found also in other myogenic genes. This may play an important role in the regulation of the protein and consequently on muscular development.   

1.
Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucl Acids Res 25:3389–3402 (1997).
2.
Arnold H, Della-Fera MA, Baile CA: Review of myostatin history, physiology and applications. LifeXY 1:1014–1022 (2001).
3.
Arthur PF: Double-muscling in cattle: a review. Aust J Agric Res 46:1493–1515 (1995).
4.
Cappuccio I, Marchitelli C, Serracchioli A, Nardone A, Valentini A: A G→T transversion induces a stop codon at the mh locus in hypertrophic Marchigiana beef subjects. Anim Genet 29:(suppl 1):51 (1998).
5.
Drysdale CMM, McGraw DW, Stack CB, Stephens JC, Judson RS, Nandabalan K, Arnold K, Ruano, G Liggett SB: Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc natl Acad Sci, USA 97:10483–10488 (2000).
6.
Ferrell RE, Conte V, Lawrence EC, Roth SM, Hagberg JM, Hurley BF: Frequent sequence variation in the human myostatin (GDF8) gene as a marker for analysis of muscle-related phenotypes. Genomics 62:203–207 (1999).
7.
Grobet L, Martin LJ, 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 Genet 17:4–5 (1997).
8.
Grobet L, Poncelet D, Royo JL, Brouwers B, Pirottin D, Michaux C, Ménissier 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. Mammal Genome 9:210–213 (1998).
9.
Heinemeyer T, Chen X, Karas H, Kel AE, Kel OV, Liebich I, Meinhardt T, Reuter I, Schacherer F, Wingender E: Expanding the TRANSFAC database towards an expert system of regulatory molecular mechanisms. Nucl Acids Res 27:318–322 (1999).
10.
Jiang YL, Li N, Du LX, Wu CX: Relationship of T→A mutation in the promoter region of myostatin gene with growth traits in swine. Yi Chuan Xue Bao 29:413–416 (2002).
11.
Kambadur R, Sharma M, Smith TPL, Bass JJ: Mutations in myostatin (GDF-8) in double muscled Belgian Blue and Piedmontese cattle. Genome Res 7:910–915 (1997).
12.
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 Genetics 31:396–399 (2001).
13.
Langley B, Thomas M, Bishop A, Sharma M, Gilmour S, Kambadur R: Myostatin inhibits myoblast differentiation by downregulating MyoD expression. J biol Chem 277:49831–49840 (2002).
14.
Lee SJ, McPherron AC. Regulation of myostatin activity and muscle growth. Proc natl Acad Sci, USA 98:9306–9311 (2001).
15.
Marchitelli C, Savarese MC, Crisà A, Valentini A: Age of myostatin alleles causing double muscling in some cattle breeds. XXVIII ISAG Congress, Göttingen, Germany, August 11–15 D083, 117 (Klar Text 2002).
16.
Marchitelli C, Savarese MC, Crisà A, Nardone A, Ajmone-Marsan P, Valentini A: Double muscling in Marchigiana beef breed is caused by a stop codon in the third exon of myostatin gene. Mammal Genome 14:392–395 (2003).
17.
McPherron AC, Lee SJ: Double muscling in cattle due to mutations in the myostatin gene. Proc natl Acad Sci, USA 94:12457–12461 (1997).
18.
Pang KM, Knecht DA: Partial inverse PCR: a technique for cloning flanking sequences. BioTechnique 22:1046–1048 (1997).
19.
Prestridge DS: Computer software for eukaryotic promoter analysis. Meth Mol Biol 130:265–295 (2000).
20.
Prestridge DS: SIGNAL SCAN 4.0: additional databases and sequence formats. Comput Appl Biosci 12:157–160 (1996).
21.
Rios R, Karneiro I, Arce VM, Devesa J: Myostatin is an inhibitor of myogenic differentiation. Am J Physiol Cell Physiol 282:C993–C999 (2002).
22.
Smith JA, Lewis AM, Wiener P, Williams JL: Genetic variation in the bovine myostatin gene in UK beef cattle: allele frequencies and haplotype analysis in the South Devon. Anim Genet 31:306–309 (2000).
23.
Spiller MP, Kambadur R, Jeanplong F, Thomas M, Martyn JK, Bass JJ, Sharma M: The myostatin gene is a downstream target gene of basic helix-loop-helix transcription factor MyoD. Mol Cell Biol 22:7066–7082 (2002).
24.
Stratil A, Kopecny M: Genomic organization, sequence and polymorphism of the porcine myostatine (GDF-8;MSTN) gene. Anim Genetics 30:462–470 (1999).
25.
Taylor WE, Bhasin S, Artaza J, Byhower F, Azam M, Willard DH Jr, Cull FC Jr, Gonzalez-Cadavid N: Myostatin inhibits cell proliferation and protein synthesis in C2C12 muscle cells. Am J Physiol Endocrinol Metab 280:E221–E228 (2001).
26.
Thomas M, Langley B, Berry C, Sharma M, Kirk S, Bass J, Kambadur R: Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation. J biol Chem 275:40235–40245 (2000).
27.
Yang H, Golenberg EM, Shoshani J: Proboscidean DNA from museum and fossil specimens: An assessment of ancient DNA extraction and amplification techniques. Biochem Genet 35:165–179 (1997).
28.
Zhang MQ: Identification of human gene core promoters in silico. Genome Res 8:319–326 (1998).
© 2003 S. Karger AG, Basel
2004
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.