A major strategy to alleviate myopathic symptoms through enhancing muscle growth and regeneration is to inhibit the action of Myostatin, a TGF -β family member that inhibits muscle growth. Presently however, no study has expanded the morphological analysis of mouse skeletal muscle beyond a few muscles of the hind limb. Therefore I have initially undertaken an expansive analysis of the skeletal musculature of the mouse forelimb and highlighted the species-specific differences with the rat. Subsequently, I examine the musculature of the forelimb in both young and old wild type and Myostatin null mice and assess the potential beneficial effects of Myostatin deletion on muscle morphology and composition with ageing. I show that the mouse muscle displays a more glycolytic phenotype compared to the rat. I demonstrate that in the absence of Myostatin, the induced myofibre hyperplasia (increase in myofibre number), hypertrophy (increase in myofibre size) and glycolytic conversion (fibre type shift towards more glycolytic phenotype) all occur in a muscle-specific manner. Next, I examine the role of Myostatin deletion on the morphology of the nerve axon. I demonstrate that skeletal muscle hyperplasia in Myostatin null mouse is accompanied by an increase in nerve fibres in major nerves of both the fore and hind limb. In addition, I show that axons within these nerves undergo hypertrophy. Furthermore, I provide evidence that the age related neural atrophic process is delayed in the absence of Myostatin. I show that skeletal muscle hyperplasia in the Myostatin null is accompanied by an increase in the number of muscle proprioceptors. Crucially, I demonstrate that absence of Myostatin reduces the amount of the extracellular matrix connective tissue. Furthermore, Myostatin deletion perturbs age-related collagen formation. Finally, I show that lack of Myostatin increases the number and the proliferation potential of satellite cells (skeletal muscle stein cell). Collectively, these data conclude that Myostatin regulates skeletal muscle development.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:553636 |
| Date | January 2011 |
| Creators | Elashry, Mohamed Ismail Elsayed |
| Publisher | University of Reading |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
Page generated in 0.002 seconds