Hostname: page-component-586b7cd67f-gb8f7 Total loading time: 0 Render date: 2024-11-24T14:33:00.538Z Has data issue: false hasContentIssue false
  • English
  • Français

The myostatin null mutation and clenbuterol administration elicit additive effects in mice

Published online by Cambridge University Press:  30 October 2009

A. C. Dilger ,
S. R. Gabriel ,
L. W. Kutzler ,
F. K. McKeith  and
J. Killefer
A. C. Dilger
Affiliation:
Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA
S. R. Gabriel
Affiliation:
Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA
L. W. Kutzler
Affiliation:
Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA
F. K. McKeith
Affiliation:
Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA
J. Killefer*
Affiliation:
Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA
*
†E-mail: [email protected]
Get access

Abstract

In mice, the myostatin (Mstn) null mutation and treatment with clenbuterol both increase muscle growth and decrease fat mass. Our objective was to determine whether mechanistic overlap exists by administering clenbuterol to Mstn null mice. Male Mstn null and wild-type mice of similar genetic backgrounds received either 0 (control) or 20 p.p.m. clenbuterol in tap water free choice for 14 days. Several traits were measured to estimate muscle and fat growth. The Mstn null mutation resulted in increased body and empty carcass weight, increased muscle weights and decreased fat pad weights. Fat content was reduced and protein content was increased in the empty carcasses of Mstn null mice. Similarly, treatment with clenbuterol resulted in increased body and empty carcass weight, increased muscle weights and reduced fat pad weights. Fat content of empty carcasses and viscera was reduced and protein content of empty carcasses was increased with clenbuterol treatment. A significant interaction of genotype and clenbuterol treatment would indicate an altered responsiveness of Mstn null mice to clenbuterol. However, only the weight of gastrocnemius muscles exhibited a significant (P = 0.01) interaction of genotype and clenbuterol treatment, indicating that Mstn null mice were less responsive to clenbuterol compared with wild-type mice. Thus, for all other traits, the impact of Mstn null mutation and clenbuterol treatment was completely additive. These data suggest that disruption of Mstn function does not alter the response of mice to β-adrenergic agonists.

Keywords

myostatin, clenbuterol, β-adrenergic agonist, mouse
Type
Full Paper
Information
animal , Volume 4 , Issue 3 , March 2010 , pp. 466 - 471
Copyright
Copyright © The Animal Consortium 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Arthur, PF 1995. Double muscling in cattle: a review. Australian Journal of Agricultural Research 46, 1493–1515.CrossRefGoogle Scholar
Association of Official Analytical Chemists (AOAC) 2000. Official methods of analysis. AOAC, Arlington, VA, USA.Google Scholar
Beermann, DH 2002. Beta-Adrenergic receptor agonist modulation of skeletal muscle growth. Journal of Animal Science 80 (suppl. 1), E18–E23.Google Scholar
Bullough, WS 1962. The control of mitotic activity in adult mammalian tissues. Biological Reviews 37, 307–342.CrossRefGoogle ScholarPubMed
Bullough, WS 1965. Mitotic and functional homeostasis: a speculative review. Cancer Research 25, 1683–1727.Google ScholarPubMed
Cubria, JC, Reguera, R, Balana-Fouce, R, Ordonez, C, Ordonez, D 1998. Polyamine-mediated heart hypertrophy induced by clenbuterol in the mouse. Journal of Pharmacy and Pharmacology 50, 91–96.CrossRefGoogle ScholarPubMed
Grobet, L, Poncelet, D, Royo, LJ, Brouwers, B, Pirottin, D, Michaux, C, Menissier, F, Zanotti, M, Dunner, S, Georges, M 1998. Molecular definition of an allelic series of mutations disrupting the myostatin function and causing double-muscling in cattle. Mammalian Genome 9, 210–213.CrossRefGoogle ScholarPubMed
Grobet, L, Royo Martin, LJ, Poncelet, D, Pirottin, D, Brouwers, B, Riquet, J, Schoeberlein, A, Dunner, S, Menissier, F, Massabanda, J 1997. A deletion in the bovine myostatin gene causes the double–muscled phenotype in cattle. Nature Genetics 17, 71–74.CrossRefGoogle ScholarPubMed
Hinkle, RT, Hodge, KM, Cody, DB, Sheldon, RJ, Kobilka, BK, Isfort, RJ 2002. Skeletal muscle hypertrophy and anti-atrophy effects of clenbuterol are mediated by the beta2-adrenergic receptor. Muscle Nerve 25, 729–734.CrossRefGoogle ScholarPubMed
Kambadur, R, Sharma, M, Smith, TP, Bass, JJ 1997. Mutations in myostatin (GDF8) in double-muscled Belgian blue and piedmontese cattle. Genome Research 7, 910–916.CrossRefGoogle ScholarPubMed
Lee, SJ 2007. Quadrupling muscle mass in mice by targeting TGF-ß signaling pathways. PLoS ONE 2, e789.CrossRefGoogle Scholar
Lee, SJ, McPherron, AC 1999. Myostatin and the control of skeletal muscle mass. Current Opinion in Genetics and Development 9, 604–607.CrossRefGoogle ScholarPubMed
Lin, J, Arnold, HB, Della-Fera, MA, Azain, MJ, Hartzell, DL, Baile, CA 2002. Myostatin knockout in mice increases myogenesis and decreases adipogenesis. Biochemical and Biophysical Research Communications 291, 701–706.CrossRefGoogle ScholarPubMed
McCroskery, S, Thomas, M, Maxwell, L, Sharma, M, Kambadur, R 2003. Myostatin negatively regulates satellite cell activation and self-renewal. Journal of Cell Biology 162, 1135–1147.CrossRefGoogle ScholarPubMed
McPherron, AC, Lawler, AM, Lee, SJ 1997. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 387, 83–90.CrossRefGoogle ScholarPubMed
McPherron, AC, Lee, SJ 1997. 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.CrossRefGoogle ScholarPubMed
McPherron, AC, Lee, S-J 2002. Suppression of body fat accumulation in myostatin-deficient mice. Journal of Clinical Investigation 109, 595–601.CrossRefGoogle ScholarPubMed
Mersmann, HJ 1998. Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action. Journal of Animal Science 76, 160–172.CrossRefGoogle ScholarPubMed
Mitchell, AD, Wall, RJ 2007. In vivo evaluation of changes in body composition of transgenic mice expressing the myostatin pro domain using dual energy X-ray absorptiometry. Growth Development and Aging 70, 25–37.Google ScholarPubMed
Novakofski, J, Park, S, Bechtel, PJ, McKeith, FK 1989. Composition of cooked pork chops: effect of removing subcutaneous fat before cooking. Journal of Food Science 54, 15–17.CrossRefGoogle Scholar
Page, KA, Hartzell, DL, Li, C, Westby, AL, Della-Fera, MA, Azain, MJ, Pringle, TD, Baile, CA 2004. Beta-adrenergic receptor agonists increase apoptosis of adipose tissue in mice. Domestic Animal Endocrinology 26, 23–31.CrossRefGoogle ScholarPubMed
Petrou, M, Wynne, DG, Boheler, KR, Yacoub, MH 1995. Clenbuterol induces hypertrophy of the Latissimus Dorsi muscle and heart in the rat with molecular and phenotypic changes. Circulation 92, 483–489.CrossRefGoogle ScholarPubMed
Reeds, PJ, Hay, SM, Dorwood, PM, Palmer, RM 1986. Stimulation of muscle growth by clenbuterol: lack of effect on muscle protein biosynthesis. British Journal of Nutrition 56, 249–258.CrossRefGoogle ScholarPubMed
Ricks, CA, Baker, PK, Dalrymple, RH 1984. Use of repartitioning agents to improve performance and body composition of meat animals. Proceedings of the reciprocal meat conference 37, 5–11.Google Scholar
Szabo, G, Dallmann, G, Muller, G, Patthy, L, Soller, M, Varga, L 1998. A deletion in the myostatin gene causes the compact (Cmpt) hypermuscular mutation in mice. Mammalian Genome 9, 671–672.Google ScholarPubMed
Thomas, M, Langley, B, Berry, C, Sharma, M, Kirk, S, Bass, J, Kambadur, R 2000. Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation. Journal of Biological Chemistry 275, 40235–40243.CrossRefGoogle ScholarPubMed
Yang, YT, McElligott, MA 1989. Multiple actions of beta-adrenergic agonists on skeletal muscle and adipose tissue. Biochemical Journal 261, 1–10.CrossRefGoogle ScholarPubMed
Yang, J, Ratovitski, T, Brady, JP, Solomon, MB, Wells, KD, Wall, RJ 2001. Expression of myostatin pro domain results in muscular transgenic mice. Molecular Reproduction and Development 60, 351–361.CrossRefGoogle ScholarPubMed
Yang, J, Zhao, B 2006. Postnatal expression of myostatin propeptide cDNA maintained high muscle growth and normal adipose tissue mass in transgenic mice fed a high-fat diet. Molecular Reproduction and Development 73, 462–469.CrossRefGoogle ScholarPubMed
Yimlamai, T, Dodd, SL, Borst, SE, Park, S 2005. Clenbuterol induces muscle-specific attenuation of atrophy through effects on the ubiquitin-proteasome pathway. Journal of Applied Physiology 99, 71–80.CrossRefGoogle ScholarPubMed
Zhao, B, Wall, RJ, Yang, J 2005. Transgenic expression of myostatin propeptide prevents diet-induced obesity and insulin resistance. Biochemical and Biophysical Research Communications 337, 248–255.CrossRefGoogle ScholarPubMed