For an in vivo assessment of skeletal muscle development in myostatin deficient mice, we have collected mouse limb muscle from many stages of development and early adulthood. We have determined the skeletal muscle precursor frequency and muscle fiber number in normal and myostatin knockout mice. We are making genetically modified mice to manipulate myostatin signaling in specific cell progenitors. We are also analyzing the function of myostatin in muscle stem cells and fibers in vitro and in vivo. To determine whether GDF11 and myostatin have redundant functions in development, we crossed GDF11 and myostatin null mice. Double mutants displayed exacerbation of the GDF11 mutant axial patterning defects demonstrating redundancy between the growth factors. To determine whether GDF11 and myostatin have redundant functions in skeletal muscle size control, we have analyzed muscle mass in mice carrying a deletion of GDF11 specifically in skeletal muscle in wild-type and myostatin null backgrounds. The muscle-specific GDF11 mutant mice have the same muscle mass, fiber number, and fiber type composition as wild-type controls. Similarly, the double muscle-specific GDF11/myostatin null mutant mice are indistinguishable from myostatin null mice demonstrating that GDF11 does not have an appreciable muscle phenotype redundant to myostatin.
