Myostatin (Mstn) is a negative regulator of skeletal muscle fibre size and satellite cell proliferation whose role in mature fibre compensatory growth has not been fully characterized. Myostatin knockout (Mstn-/-) mice display consistently larger skeletal muscle masses, as well as an overall increase in size and number of myofibres within the muscle, compared to the wild-type mice. Previous research has shown that Mstn plays a major role in the attenuation of both the hypertrophic and hyperplasic pathways of myofibre growth. Immunohistochemical staining of overloaded plantaris muscles was performed to analyze phenotypic and morphological changes in wild-type and Mstn-/- muscles. Preliminary results of these analyses indicated a tendency for muscles from Mstn-/- mice to express an increased number of myofibres, whereas muscles from Mstn+/+ mice tended to display hypertrophied pre-existing mature myofibres as a response to the overload stimulus. Additionally, using semi-quantitative PCR and western blotting, changes were monitored, in mRNA transcripts and protein expression levels, for some of the major factors involved in muscle growth signalling. Our preliminary results also showed altered expression of genes and proteins that ultimately translate to increased satellite cell proliferation and maturation in Mstn-/- muscles. Taken together, myostatin's effect on muscle is most apparent in attenuating the hyperplasic growth response in stimulated muscle, and not the hypertrophic signalling pathway. This is the first in vivo study to specifically look at the function of myostatin in muscles that are induced to grow by means of functional overloading
