Muscle growth after post-developmental myostatin gene knockout

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Am J Physiol Endocrinol Metab. 2006 Dec 5

Muscle growth after post-developmental myostatin gene knockout.

Welle S, Bhatt K, Pinkert CA, Tawil R, Thornton CA.

Medicine, University of Rochester, Rochester, New York, United

States.

Constitutive myostatin gene knockout in mice causes excessive muscle

growth during development.

To examine the effect of knocking out the myostatin gene after

muscle has matured, we generated mice in which myostatin exon 3 was

flanked by loxP sequences (Mstn[f/f]) and crossed them with mice

bearing a tamoxifen-inducible, ubiquitously-expressed Cre

recombinase transgene.

At 4 months of age, Mstn[f/f]/Cre+ mice that had not received

tamoxifen had a 50-90% reduction in myostatin expression due to

basal Cre activity, but were not hypermuscular relative to Mstn

[w/w]/Cre+ mice (homozygous for wild-type myostatin gene). Three

months after tamoxifen treatment (initiated at 4 months of age),

muscle mass had not changed from the pre-treatment level in Mstn

[w/w]/Cre+ control mice.

Tamoxifen administration to 4 month old Mstn[f/f]/Cre+ mice reduced

myostatin mRNA expression to less than 1% of normal, which increased

muscle mass ~25% over the following 3 months in both male and female

mice (P < 0.005 vs. control). Fiber hypertrophy appeared to be

sufficient to explain the increase in muscle mass. The pattern of

expression of genes encoding the various myosin heavy chain isoforms

was unaffected by post-developmental myostatin knockout.

Conclusion: even after developmental muscle growth has ceased,

knockout of the myostatin gene induces a significant increase in

muscle mass.