For an in vivo assessment of skeletal muscle development in myostatin deficient mice, we have determined the skeletal muscle precursor frequency and muscle fiber number in normal and myostatin knockout mice. We have also shown that myostatin inhibition in adult mice in vivo causes very little activation of muscle stem cells. This demonstrates that myostatin inhibition increases muscle mass in adults mainly by causing hypertrophy of myofibers rather than activation of satellite cells. We are making genetically modified mice to manipulate myostatin signaling in specific cell progenitors using the inducible tetracycline system. Several transgenic mouse lines have been generated and are being analyzed for skeletal muscle phenotypes.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2012
Total Cost
$406,660
Indirect Cost
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Manoli, Irini; Kwan, Justin Y; Wang, Qian et al. (2013) Chronic myopathy due to immunoglobulin light chain amyloidosis. Mol Genet Metab 108:249-54
Wang, Qian; McPherron, Alexandra C (2012) Myostatin inhibition induces muscle fibre hypertrophy prior to satellite cell activation. J Physiol 590:2151-65
Lipina, Christopher; Kendall, Hannah; McPherron, Alexandra C et al. (2010) Mechanisms involved in the enhancement of mammalian target of rapamycin signalling and hypertrophy in skeletal muscle of myostatin-deficient mice. FEBS Lett 584:2403-8
Savage, Kathleen J; McPherron, Alexandra C (2010) Endurance exercise training in myostatin null mice. Muscle Nerve 42:355-62
Cash, Jennifer N; Rejon, Carlis A; McPherron, Alexandra C et al. (2009) The structure of myostatin:follistatin 288: insights into receptor utilization and heparin binding. EMBO J 28:2662-76
McPherron, Alexandra C; Huynh, Thanh V; Lee, Se-Jin (2009) Redundancy of myostatin and growth/differentiation factor 11 function. BMC Dev Biol 9:24