Induction of cachexia in mice by systemically administered myostatin.
Mice and cattle with genetic deficiencies in myostatin exhibit dramatic increases in skeletal muscle mass, suggesting that myostatin normally suppresses muscle growth. Whether this increased muscling results from prenatal or postnatal lack of myostatin activity is unknown. Here we show that myostatin circulates in the blood of adult mice in a latent form that can be activated by acid treatment. Systemic overexpression of myostatin in adult mice was found to induce profound muscle and fat loss analogous to that seen in human cachexia syndromes. These data indicate that myostatin acts systemically in adult animals and may be a useful pharmacologic target in clinical settings such as cachexia, where muscle growth is desired.
Zimmers
Teresa A
TA
Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Davies
Monique V
MV
Koniaris
Leonidas G
LG
Haynes
Paul
P
Esquela
Aurora F
AF
Tomkinson
Kathy N
KN
McPherron
Alexandra C
AC
Wolfman
Neil M
NM
Lee
Se-Jin
SJ
D016475:3T3 Cells; D028341:Activins / Q000008:administration & dosage / Q000494:pharmacology; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000473:pathology; D000818:Animals; D001835:Body Weight; D016466:CHO Cells; D002100:Cachexia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006224:Cricetinae; D004435:Eating; D005260:Female; D038681:Follistatin; D008099:Liver / Q000033:anatomy & histology / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000473:pathology; D018482:Muscle, Skeletal / Q000033:anatomy & histology* / Q000473:pathology; D055435:Myostatin; D009929:Organ Size; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D011994:Recombinant Proteins / Q000008:administration & dosage; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D019282:Wasting Syndrome / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D015431:Weight Loss
D038681:Follistatin; C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin; D010446:Peptide Fragments; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D028341:Activins