Effects of the Compact Mutant Myostatin Allele Mstn Cmpt-dl1Abc Introgressed into a High Growth Mouse Line on Skeletal Muscle Cellularity

  • Charlotte Rehfeldt
  • Gerhard Ott
  • David E. Gerrard
  • László Varga
  • Werner Schlote
  • John L. Williams
  • Ulla Renne
  • Lutz Bünger


The murine myostatin mutation MstnCmpt-dl1Abc (Compact; C) was introduced into an inbred mouse line with extreme growth (DUHi) by marker-assisted introgression. To study the allelic effects on muscle fibre hyperplasia and hypertrophy, myonuclear proliferation, protein accretion, capillary density, and muscle fibre metabolism, samples from M. rectus femoris (RF) and M. longissimus dorsi (LD) muscles of animals wild-type (+/+), heterozygous (C/+), and homozygous (C/C) for the MstnCmpt-dl1Abc allele were examined by histological and biochemical analyses. Homozygous C/C mice exhibited lower body (−12%) but higher muscle weights (+38%) than ++ mice. Total muscle fibre number was increased (+24%), whereas fibre size was not significantly affected. Protein and DNA concentrations and DNA:protein ratios as well as specific CK activity remained unchanged for higher mass muscle implying increases in the total contents of DNA and muscle specific protein. Fibre type distribution was markedly shifted to the white glycolytic muscle fibres (+16–17% units) at the expense of red oxidative fibres. Capillary density was substantially lower in C/C than in ++ mice as seen by lower number of capillaries per fibre (−35%) and larger fibre area per capillary (+77%). However, the MstnCmpt-dl1Abc allele was partially recessive in heterozyogous C/+ mice for both fibre type frequencies and capillary density. The results show that hypermuscularity caused by mutations in the myostatin gene results from muscle fibre hyperplasia rather than hypertrophy, and from balanced increases in myonuclear proliferation and protein accretion. However, capillary supply is adversely affected and muscle metabolism shifted towards glycolysis, which could have negative consequences for physical fitness.


Capillary Density Rectus Femoris Longissimus Dorsi Myostatin Gene Fibre Type Distribution 
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  1. Amthor, H, Huang, R, McKinnell, I, Christ, B, Kambadur, R, Sharma, M, Patel, K 2002The regulation and action of myostatin as a negative regulator of muscle development during avian embryogenesisDev Biol251241257PubMedCrossRefGoogle Scholar
  2. Arnold, HA, Della-Fera, MA, Baile, CA 2001Review of myostatin history, physiology and applicationsInt Arch Biosci200110141022Google Scholar
  3. Arthur, PF 1995Double muscling in cattle: a review.Austr J Agricult Res4614931515Google Scholar
  4. Barkemeyer, H, Horst, P 1990Consequences of long-term selection for protein deposition on growth of mice [in German, English summary]J Anim Breed Genet1075260Google Scholar
  5. Bünger, L, Laidlaw, AH, Bulfield, G, Eisen, EJ, Medrano, JF, Bradford, GE, Pirchner, F, Renne, U, Schlote, W, Hill, WG 2001Inbred lines of mice derived from long-term on growth selected lines: unique resources for mapping growth genesMamm Genome12678686PubMedGoogle Scholar
  6. Bünger, L, Renne, U, Buis, RC 2001bBody weight limits in mice - long-term selection and single genesReeve, ECR eds. Encyclopedia of GeneticsFitzroy Dearborn PublishersLondon Chicago337360Google Scholar
  7. Bünger L, Ott G, Varga L, Schlote W, Rehfeldt C, Williams JL and Hill WG (2004) <A NAME="OLE">Marker assisted introgression of the Compact mutant myostatin allele: MstnCmpt-dl1Abc into a mouse line with extreme growth-effects on body composition and muscularity. Genet Res Google Scholar
  8. Bünger, L, Renne, U, Dietl, G, Kuhla, S 1998Long-term selection for protein amount over 70 generations in miceGenet Res7293109PubMedGoogle Scholar
  9. Degens, H, Turek, Z, Hoofd, LJ, Van’t Hof, MA, Binkhorst, RA 1992The relationship between capillarisation and fibre types during compensatory hypertrophy of the plantaris muscle in the ratJ Anat180455463PubMedGoogle Scholar
  10. Dimauro, J, Balnave, RJ, Shorey, CD 1992Effects of anabolic steroids and high intensity exercise on rat skeletal muscle fibres and capillarization. A morphometric studyEur J Appl Physiol64204212CrossRefGoogle Scholar
  11. 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 1997A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattleNat Genet177174PubMedCrossRefGoogle Scholar
  12. Grobet, L, Pirottin, D, Farnir, F, Poncelet, D, Royo, LJ, Brouwers, B, Christians, E, Desmecht, D, Coignoul, F, Kahn, R, Georges, M 2003Modulating skeletal muscle mass by postnatal, muscle-specific inactivation of the myostatin geneGenesis35227238PubMedCrossRefGoogle Scholar
  13. Hather, BM, Mason, CE, Dudley, GA 1991Histochemical demonstration of skeletal muscle fibre types and capillaries on the same transverse sectionClin Physiol11127134PubMedGoogle Scholar
  14. Holmes, JH, Ashmore, CR 1972A histochemical study of development of muscle fibre type and size in normal and double muscled cattleGrowth36351372PubMedGoogle Scholar
  15. Holmes, JH, Ashmore, CR, Robinson, DW 1973Effects of stress on cattle with heriditary muscular hypertrophyJ Anim Sci36684694PubMedGoogle Scholar
  16. Horst P, Steinhauf D, Weniger JH, Tawfik ES and Major F (1975) Modellversuch zur Selektion auf Belastbarkeit in ihrer Beziehung zum Wachstum. 2. Selektionsergebnisse bis zur 10. Selektionsgeneration. J Anim Breed Genet 92: 260–266.Google Scholar
  17. Jensen, L, Bangsbo, J, Hellsten, Y 2004Effect of high intensity training on capillarisation and presence of angiogenic factors in human skeletal muscleJ Physiol557571582PubMedCrossRefGoogle Scholar
  18. Kambadur, R, Sharma, M, Smith, TP, Bass, JJ 1997Mutations in myostatin (GDF8) in double-muscled Belgian Blue and Piedmontese cattleGenome Res7910916PubMedGoogle Scholar
  19. Kuhn, G, Rehfeldt, C, Ender, K 2002Heavy newborn piglets develop a high carcass quality [in German, English summary]Fleischwirtsch82128129Google Scholar
  20. Langley, B, Thomas, M, Bishop, A, Sharma, M, Gilmour, S, Kambadur, R 2002Myostatin inhibits myoblast differentiation by down-regulating MyoD expressionJ Biol Chem2774983149840PubMedCrossRefGoogle Scholar
  21. McPherron, AC, Lawler, AM, Lee, SJ 1997Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily memberNature3878390PubMedCrossRefGoogle Scholar
  22. McPherron, AC, Lee, SJ 1997Double muscling in cattle due to mutations in the myostatin geneProc Natl Acad Sci USA941245712461PubMedCrossRefGoogle Scholar
  23. Moss, FP, Leblond, CP 1971Satellite cells as the source of nuclei in muscle of growing ratsAnat Rec170421436PubMedCrossRefGoogle Scholar
  24. Nishi, M, Yasue, A, Nishimatu, S, Nohno, T, Yamaoka, T, Itakura, M, Moriyama, K, Ohuchi, H, Noji, S 2002A missense mutant myostatin causes hyperplasia without hypertrophy in the mouse muscleBiochem Biophys Res Commun293247251PubMedCrossRefGoogle Scholar
  25. Novikoff, AB, Shin, W, Drucker, J 1961Mitochondrial localization of oxidative enzymes staining results with two tetrazolium saltsJ Biophys Biochem Cytol94761PubMedCrossRefGoogle Scholar
  26. Ouhayoun, J, Beaumont, A 1968Etude du caractère culard: III. Anatomic microscopique comparée du tissu musculaire de mâle charolais normeaux et culardsAnn Zootech17213223Google Scholar
  27. Rehfeldt, C, Bünger, L 1983Adaptation of laboratory mice skeletal muscle fibres to endurance training, confinement or selection for body weight and endurance fitness [in German, English summary]Z mikrosk-anat Forsch9792102PubMedGoogle Scholar
  28. Rehfeldt, C, Bünger, L 1990Effects of long-term selection of laboratory mice on parameters of muscle growth and muscle structure [in German, English summary]Arch Tierz33507516Google Scholar
  29. Rehfeldt, C, Fiedler, I, Dietl, G, Ender, K 2000Myogenesis and postnatal skeletal muscle cell growth as influenced by selectionLivest Prod Sci66177188CrossRefGoogle Scholar
  30. Rehfeldt C, Fiedler I and Stickland NC (2004) Number and size of muscle fibres in relation to meat production. In: Te Pas, Haagsman and Everts (eds) Muscle Development of Livestock Animals: Physiology, Genetics and Meat Quality. (pp. 1–37) CAB Intl., Wallingford, Oxon, UK.Google Scholar
  31. Rehfeldt C and Walther K (1997) A combined assay for DNA, protein and incorporated [3 H] label in cultured muscle cells. Anal Biochem 251: 294–297.Google Scholar
  32. Schadereit, R, Rehfeldt, C, Krawielitzki, K, Klein, M, Kanitz, E, Kuhla, S 1998Protein turnover, body composition, muscle characteristics and blood hormones in response to different direction of growth selection in miceJ Anim Feed Sci7333352Google Scholar
  33. Schultz, EA 1974A quantitative study of satellite cell population in postnatal mouse lumbrical muscleAnat Rec180589596PubMedCrossRefGoogle Scholar
  34. Shahin, K, Berg, RT 1985Growth patterns of muscle, fat and bone and carcass composition of double muscled and normal cattleCan J Anim Sci65279294Google Scholar
  35. Smith, PK, Krohn, RI, Hermanson, GT, Mallia, AK, Gartner, FH, Provenzano, MD, Fujimoto, EK, Goeke, NM, Olson, BJ, Klenk, DC 1985Measurement of protein using bicinchoninic acidAnal Biochem1507685PubMedCrossRefGoogle Scholar
  36. Spannhof, L 1967Einführung in die Praxis der HistochemieVEB Gustav-Fischer-VerlagJena172Google Scholar
  37. Stickland, NC, Bayol, S, Ashton, C, Rehfeldt, C 2004Manipulation of muscle fibre numberTe, PasHaagsman, Everts,  eds. Muscle Development of Livestock Animals: Physiology, Genetics and Meat Quality. CAB Intl.WallingfordOxton, UK6982Google Scholar
  38. Szabo, G, Dallmann, G, Müller, G, Patthy, L, Soller, M, Varga, L 1998A deletion in the myostatin gene causes the compact (Cmpt) hypermuscular mutation in miceMamm Genome9671672PubMedGoogle Scholar
  39. Taylor, WE, Bhasin, S, Artaza, J, Byhower, F, Azam, M, Willard, DH,Jr, Kull, FC,Jr, Gonzalez-Cadavid, N 2001Myostatin inhibits cell proliferation and protein synthesis in C2C12 muscle cellsAm J␣Physiol Endocrinol Metabol80E221E228Google Scholar
  40. Terjung, RL, Zarzeczny, R, Yang, HT 2002Muscle blood flow and mitochondrial function: influence of agingInt J Sport Nutr Exerc Metab12368378PubMedGoogle Scholar
  41. Thomas, M, Langley, B, Berry, C, Sharma, M, Kirk, S, Bass, J, Kambadur, R 2000Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferationJ Biol Chem2754023540243PubMedGoogle Scholar
  42. Valle Zarate, A, Horst, P, Weniger, JH 1994Antagonism between growth and productive adaptability in mice [in German, English summary]Arch Tierz37185198Google Scholar
  43. Varga, L, Müller, G, Szabo, G, Pinke, O, Korom, E, Kovacs, B, Patthy, L, Soller, M 2003Mapping modifiers affecting muscularity of the myostatin mutant (MstnCmpt-dl1Abc) Compact mouseGenetics165257267PubMedGoogle Scholar
  44. Varga, L, Szabo, G, Darvasi, A, Müller, G, Sass, M, Soller, M 1997Inheritance and mapping of compact (cmpt), a new mutation causing hypermuscularity in miceGenetics147755764PubMedGoogle Scholar
  45. Wegner, J, Albrecht, E, Fiedler, I, Teuscher, F, Papstein, H-J, Ender, K 2000Growth and breed-related changes of muscle fiber characteristics in cattleJ Anim Sci7814851496PubMedGoogle Scholar
  46. Weniger, JH, Horst, P, Steinhauf, D, Major, F, Wolf, M, Tawfik, ES 1974Model experiments on selection for endurance and its relation to growth. Part I. Introduction, methods and preliminary investigations on the basic population [in German, English summary]J Anim Breed Genet91265270Google Scholar
  47. West, RL 1974Red to white fibre ratios as an index of double muscling in beef cattleJ Anim Sci3811651175PubMedGoogle Scholar
  48. Zhu, X, Hadhazy, M, Wehling, M, Tidball, JG, McNally, EM 2000Dominant negative myostatin produces hypertrophy without hyperplasia in muscleFEBS Lett4747175PubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Charlotte Rehfeldt
    • 1
  • Gerhard Ott
    • 2
  • David E. Gerrard
    • 3
  • László Varga
    • 4
  • Werner Schlote
    • 5
  • John L. Williams
    • 6
  • Ulla Renne
    • 1
  • Lutz Bünger
    • 7
  1. 1.Department of Muscle Biology and GrowthResearch Institute for the Biology of Farm AnimalsDummerstorfGermany
  2. 2.Fachhochschule Lippe – University of Applied SciencesLemgoGermany
  3. 3.Department of Animal SciencesPurdue UniversityWest LafayetteUSA
  4. 4.Agricultural Biotechnology CenterGödöllöHungary
  5. 5.Landwirtschaftlich-Gärtnerische Fakultät, Institut für Nutztierwissenschaften, PopulationsgenetikHumboldt-Universität zu BerlinBerlinGermany
  6. 6.Roslin Institute (Edinburgh)Roslin MidlothianUK
  7. 7.Institute of Cell, Animal and Population BiologyUniversity of EdinburghEdinburghUK

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