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.