| Myostatin is an important negative regulator of muscle mass. Disruption of the myostatin gene leads to dramatic increases of skeletal muscle mass. Skeletal muscle is highly plastic and adapts in response to changes in workload, activity and pathological conditions. In this thesis, I set out to investigate the underlying mechanisms involved in growth in the absence of myostatin. We used the myostatin knockout model in combination with synergist ablation or denervation to study growth and atrophy.;During growth induced by functional overload, skeletal muscles increase their mass, midbelly and fiber cross-sectional area (CSA), and protein synthesis. The rapid growth also induces the activation and proliferation of satellite cells. In skeletal muscle, functional overload in myostatin knockout mice led to reduced growth in muscle mass and fiber size and a blunted switch of muscle fibers metabolic profile to a slower phenotype compared to their wildtype counterpart. Additionally, the distal portion of the plantaris was a region of major remodeling in both groups. Denervation through sciatic nerve section is an effective method to induce muscle atrophy. Following denervation, a rapid loss in muscle mass and fiber size occurs. Absence of myostatin did not prevent muscle mass and CSA loss in response to denervation. Moreover, no changes in the expression of MyHC isoforms were found.;In conclusion, myostatin is not the only regulator skeletal muscle mass. In its absence, alternative strategies are employed to reach a different outcome of growth and no protection from muscle atrophy was observed suggesting other mechanisms at play. |
