Lack of myostatin in mice results in excessive muscle but impaired force generation, tubular aggregates and alterations in fibre type profile

Loss of myostatin stimulates the growth of skeletal muscle, and strategies that suppress myostatin activity have been proposed as a treatment for various muscle wasting disorders. To further understand the impact of the lack of myostatin on muscle performance, we have examined the functional and histological properties of the extensor digitorum longus (EDL) of constitutive myostatin knockout mice. We report that despite a larger muscle mass relative to age matched controls, there was no increase in maximum tetanic force generation such that when force generation was expressed as a function of muscle size (specific force), the EDL from myostatin knockout mice generated significantly less force relative to wild type muscle. In addition, the EDL from myostatin knockout mice showed a faster contraction and relaxation and a marked increase in the number of IIb fibres relative to wild type controls. Furthermore, an abundance of tubular aggregates in type IIb muscle fibres were found in both male and female myostatin knockout mice. Overall, our results suggest that the loss of myostatin compromises force production by mechanisms yet to be identified and that further studies on animal models are necessary prior to trials of myostatin blockade on patients suffering from muscle wasting disorders.