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Abstract
Dystrophin and α-actinin-3 are two proteins found within, or in close association with, the Z-disc of skeletal muscle. Dystrophin deficiency results in the condition of Duchenne muscular dystrophy, while α-actinin-3 deficiency impairs athletic performance in sprint and power activities. Because of their location and protein interactions, and the observed effects of their deficiency in humans, they are most commonly perceived as having structural roles within muscle. This thesis attempts to gain insight into whether their roles are purely structural, or whether they may have more complex functions. Using dystrophin-deficient mdx mice, this thesis found that muscles with a greater degree of morphological deformity (fibre branching) showed a greater loss of force following eccentric (lengthening) contractions. This result indicates that evidence previously used to argue in favour of a structural role for dystrophin may have been confounded by the presence of deformed fibres. This thesis also characterised the phenotype of the Actn3 knockout mouse, a newly generated model of α-actinin-3 deficiency. The phenotype was examined at whole muscle and skinned fibre levels. Actn3 knockout muscles showed changes indicative of a shift from fast fibre-type properties towards slower fibre-type properties in the absence of α-actinin-3. These results suggest a possible role for α-actinin-3 in promoting the differentiation of fast-twitch, glycolytic properties in muscle fibres.