Molecular definition of an allelic series of mutations disrupting the myostatin function and causing double-muscling in cattle

Grobet, Luc; Poncelet, Dominique; Royo, Luis J.; Brouwers, Benoît; Pirottin, Dimitri; Michaux, Charles; Ménissier, François; Zanotti, M.; Dunner, S.; Georges, Michel

doi:10.1007/s003359900727

Cited by 410 publications

(325 citation statements)

References 13 publications

Supporting

Mentioning

300

Contrasting

Unclassified

Order By: Relevance

“…Myostatin then has to be released from this latent complex to be active. Indeed, the specificity of myostatin is evident in myostatin-null animals, where the altered phenotype is restricted exclusively to skeletal muscle (Kambadur et al, 1997;Grobet et al, 1998;Zhu et al, 2000).…”

Section: Rd Cell Growth Is Inhibited By Myostatinmentioning

confidence: 99%

“…The deletion of myostatin in mice, mutations in the myostatin gene in Belgian Blue and Piedmontese cattle or the perturbation of myostatin function all result in increased skeletal muscle mass (Kambadur et al, 1997;Grobet et al, 1998;Szabo et al, 1998;Zhu et al, 2000;Yang et al, 2001). Like other TGF-b family members, myostatin appears to be synthesized as a precursor molecule, which is subsequently cleaved to generate an N-terminal propeptide or latency-associated peptide (LAP) and a Cterminal active peptide or mature myostatin.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Myostatin inhibits rhabdomyosarcoma cell proliferation through an Rb-independent pathway

et al. 2004

View full text Add to dashboard Cite

Rhabdomyosarcoma (RMS) tumors are the most common soft-tissue sarcomas in childhood. In this investigation, we show that myostatin, a skeletal muscle-specific inhibitor of growth and differentiation is expressed and translated in the cultured RMS cell line, RD. The addition of exogenous recombinant myostatin inhibits the proliferation of RD cells cultured in growth media, consistent with the role of myostatin in normal myoblast proliferation inhibition. However, unlike normal myoblasts, upregulation of p21 was not observed. Rather, myostatin signalling resulted in the specific downregulation of both Cdk2 and its cognate partner, cyclin-E. The analysis of Rb reveals that there was no change in its phosphorylation status with myostatin treatment, consistent with D-type-cyclinCdk4/6 complexes being active in the absence of p21. Moreover, the activity of Rb appeared to be unchanged between treated and nontreated RD cells, as determined by the ability of Rb to bind E2F1. The examination of NPAT, a substrate of cyclin-E-Cdk2 involved in the transcriptional activation of replication-dependent histone gene expression, revealed that it undergoes a loss of phosphorylation with myostatin treatment. Supporting this, a downregulation in H4-histone gene expression was observed. These results suggest that myostatin could potentially be used as an inhibitor of RMS proliferation and define a previously uncharacterized, Rb-independent mechanism for the inhibition of muscle precursor cell proliferation by myostatin.

show abstract

Section: Rd Cell Growth Is Inhibited By Myostatinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Myostatin inhibits rhabdomyosarcoma cell proliferation through an Rb-independent pathway

et al. 2004

View full text Add to dashboard Cite

show abstract

“…The double-muscled Belgian Blue breed (the dominant breed in the Belgian beef industry) is assumed to be more susceptible to heat stress than most other beef breeds (Halipre, 1973), owing to reduced oxygen transport efficiency (Lekeux et al, 2009) and reduced pulmonary and cardiac function (Gustin et al, 1988;Amory et al, 1992). This is caused by the relatively small volume of heart and lungs (in comparison with the body volume) and the aberrant myostatin gene (Grobet et al, 1998). Research on heat stress in Belgian Blue beef cattle is limited, however, to field studies on the sheltering behaviour of Belgian pastoral beef cattle (Rosselle et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Effect of summer conditions and shade on behavioural indicators of thermal discomfort in Holstein dairy and Belgian Blue beef cattle on pasture

laer¹,

Moons

Ampe³

et al. 2015

Animal

View full text Add to dashboard Cite

Using behavioural indicators of thermal discomfort, that is, shade seeking, panting scores (PS) and respiration rate (RR), we evaluated the effect of hot summer conditions and shade, for a herd of adult Holstein dairy cows and a herd of Belgian Blue beef cows kept on pasture in a temperate area (Belgium). During the summer of 2012, both herds were kept on pasture without access to shade (NS). During the summers of 2011 and 2013 each herd was divided into one group with (S) and one without (NS) access to shade. Shade was provided by young trees with shade cloth (80% reduction in solar radiation) hung between them. For S cows, we investigated how shade use was related to hot conditions as quantified by six climatic indices. The heat load index (HLI), which incorporates air temperature and humidity, solar radiation and wind speed, was the best predictor of the six indices tested. In 2011, there was a relatively high threshold for use of shade. When HLI = 90, shade use probability reached 17% for dairy cows and 27% for beef cows. In 2013, however, at HLI = 90, shade use probability reached 48% for dairy cows and 41% for beef cows. For animals from the NS treatment we determined the effect of hot summer conditions on RR and PS (with 0 = no panting and 4.5 = extreme panting). In both types of cattle, an increase in black globe temperature was the best predictor for increasing RR and PS. Furthermore, we determined how the effect of hot summer conditions on RR and PS was affected by the use of shade. Under hot conditions (black globe temperature ⩾ 30°C), >50% of the animals under shade retained normal PS and RR (PS < 1 and RR < 90 breaths per minute), whereas normal RR and PS were significantly less prevalent for animals outside shade. Our findings suggest that, even in temperate summers, heat can induce thermal discomfort in cattle, as evidenced by increases in shade use, RR and PS, and that shade increases thermal comfort.

show abstract

“…Another strategy to alter animal growth is to introduce mutations into the Mstn gene as occurs naturally in double-muscled cattle. These cattle exhibit striking increases in muscle growth and reductions in fat mass (Grobet et al, 1997;Kambadur et al, 1997;Grobet et al, 1998). Transgenic Mstn null mice can be used as a model for this effect as this species also exhibits increased muscularity and decreased fat deposition McPherron and Lee, 2002).…”

Section: Introductionmentioning

confidence: 99%

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

Dilger

Gabriel

Kutzler

et al. 2010

Animal

View full text Add to dashboard Cite

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 5 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 b-adrenergic agonists.

show abstract

Molecular definition of an allelic series of mutations disrupting the myostatin function and causing double-muscling in cattle

Cited by 410 publications

References 13 publications

Myostatin inhibits rhabdomyosarcoma cell proliferation through an Rb-independent pathway

Myostatin inhibits rhabdomyosarcoma cell proliferation through an Rb-independent pathway

Effect of summer conditions and shade on behavioural indicators of thermal discomfort in Holstein dairy and Belgian Blue beef cattle on pasture

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

Contact Info

Product

Resources

About