Expression of myostatin pro domain results in muscular transgenic mice.
Myostatin, a member of the TGF-beta family, negatively regulates skeletal muscle development. Depression of myostatin activity leads to increased muscle growth and carcass lean yield. In an attempt to down-regulate myostatin, transgenic mice were produced with a ribozyme-based construct or a myostatin pro domain construct. Though the expression of the ribozyme was detected, muscle development was not altered by the ribozyme transgene. However, a dramatic muscling phenotype was observed in transgenic mice carrying the myostatin pro domain gene. Expression of the pro domain transgene at 5% of beta-actin mRNA levels resulted in a 17-30% increase in body weight (P < 0.001). The carcass weight of the transgenic mice showed a 22-44% increase compared with nontransgenic littermates at 9 weeks of age (16.05 +/- 0.67 vs. 11.16 +/- 0.28 g in males; 9.99 +/- 0.38 vs. 8.19 +/- 0.19 g in females, P < 0.001). Extreme muscling was present throughout the whole carcass of transgenic mice as hind and fore limbs and trunk weights, all increased significantly (P < 0.001). Epididymal fat pad weight, an indicator of body fat, was significantly decreased in pro domain transgenic mice (P < 0.001). Analysis of muscle morphology indicated that cross-sectional areas of fast-glycolytic fibers (gastrocnemius) and fast-oxidative glycolytic fibers (tibialis) were larger in pro domain transgenic mice than in their controls (P < 0.01), whereas fiber number (gastrocnemius) was not different (P > 0.05). Thus, the muscular phenotype is attributable to myofiber hypertrophy rather than hyperplasia. The results of this study suggest that the over-expression of myostatin pro domain may provide an alternative to myostatin knockouts as a means of increasing muscle mass in other mammals.
Yang
J
J
Gene Evaluation and Mapping Laboratory, USDA-ARS, 10300 Baltimore Avenue, Beltsville, MD 20705-2350, USA.
Ratovitski
T
T
Brady
J P
JP
Solomon
M B
MB
Wells
K D
KD
Wall
R J
RJ
D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006984:Hypertrophy; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D018994:Myosin Light Chains / Q000235:genetics; D055435:Myostatin; D010641:Phenotype; D017434:Protein Structure, Tertiary; D016337:RNA, Catalytic / Q000235:genetics; D051381:Rats; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics*
C525912:Mstn protein, mouse; C525913:Mstn protein, rat; D018994:Myosin Light Chains; D055435:Myostatin; D016337:RNA, Catalytic; D016212:Transforming Growth Factor beta