Muscle growth regulation

Subproject Speakers

Berlin: Markus Schülke-Gerstenfeld, MD, Prof.
Paris / Versailles: Helge Amthor, MD, Prof. / Luis Garcia, PhD, Prof.

In normal individuals, several signaling molecules of the transforming growth factor beta (TGF-β) family, most notably myostatin, restrict the size of skeletal muscle. The precise function of myostatin remains unclear. We hypothesize that myostatin optimizes function and metabolism of skeletal muscle. Most previous work exploring the function of myostatin has been performed on constitutive myostatin knockout mice, which does not permit a differentiation between the prenatal or postnatal effect of myostatin deficiency. Moreover, up to date, the role of myostatin on muscle function and metabolism has only been explored in lack-of-function models. Our aim is to determine the function of myostatin on skeletal muscle physiology and metabolism in adult wildtype mice using gain-of-function and loss-of-function models. We will therefore be able judge the effect of myostatin modulation in the context of novel biotherapies and also in the context of a potential abuse for athletic "doping" purposes. To this end, we will directly compare the effect of myostatin induced muscle hypotrophy (treatment with recombinant myostatin) with the effect of myostatin blockade induced muscle hypertrophy (treatment with AAV myostatin propeptide). We will compare the effect on force generation, exercise capacity, oxidative muscle metabolism, muscle morphometry and cellular properties.

Theses in progress

Completed theses