Myostatin-deficient mice lose more skeletal muscle mass than wild-type controls during hindlimb suspension.
Myostatin inhibits myogenesis. Therefore, we sought to determine if mice lacking the myostatin gene [Mstn(-/-)] would lose less muscle mass than wild-type mice during 7 days of hindlimb suspension (HS). Male Mstn(-/-) and wild-type (C57) mice were subjected to HS or served as ground-based controls (n = 6/group). Wild-type mice lost 8% of body mass and approximately 13% of wet mass from biceps femoris, quadriceps femoris, and soleus, whereas the mass of extensor digitorum longus (EDL) was unchanged after HS. Unexpectedly, Mstn(-/-) mice lost more body (13%, P < 0.05) and quadriceps femoris (17%, P < 0.05) mass than wild-type mice and lost 33% of EDL mass (P < 0.01) after HS. Protein expression of myostatin in biceps femoris and quadriceps femoris was not altered, whereas expression of MyoD, Myf-5, and myogenin increased in wild-type mice and tended to decrease in muscles of Mstn(-/-) mice. These data suggest that HS induced myogenesis in wild-type mice to counter atrophy, whereas myogenesis was not induced in Mstn(-/-) mice, thereby resulting in a greater loss of muscle mass.
McMahon
Christopher D
CD
Functional Muscle Genomics, AgResearch Limited, Ruakura Agricultural Centre, Hamilton, New Zealand. chris.mcmahon@agresearch.co.nz
Popovic
Ljiljana
L
Oldham
Jenny M
JM
Jeanplong
Ferenc
F
Smith
Heather K
HK
Kambadur
Ravi
R
Sharma
Mridula
M
Maxwell
Linda
L
Bass
James J
JJ
D000818:Animals; D001284:Atrophy / Q000473:pathology; D015415:Biomarkers; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D004268:DNA-Binding Proteins; D019417:Hindlimb Suspension / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000502:physiology*; D017570:MyoD Protein / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin / Q000378:metabolism; D055435:Myostatin; D009929:Organ Size / Q000502:physiology; D015534:Trans-Activators; D016212:Transforming Growth Factor beta / Q000172:deficiency* / Q000235:genetics
D015415:Biomarkers; D004268:DNA-Binding Proteins; C525912:Mstn protein, mouse; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; C503801:Myog protein, mouse; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D055435:Myostatin; D015534:Trans-Activators; D016212:Transforming Growth Factor beta