The muscle and neuronal isoforms can be further characterized by three unique Nterminal regions that influence the subcellular localization of these proteins. The dystonin-b muscle isoforms are the largest and consist of several domains: an N-terminal actin-binding domain, a plakin domain, a spectrin repeat containing rod domain, a centrally located intermediate filament binding domain and a microtubule-binding domain at the C-terminus. The dystonia musculorum mouse mutant has been studied as a model of sensory neuropathy since its initial identification. Several allelic variants of dt exist in which mutations of the dystonin gene result in a dramatic reduction and virtual loss of dystonin gene expression. In the dtTg4 mouse model, intrinsic skeletal muscle defects have previously been reported. Specifically, skeletal muscles from the dtTg4 mice have thick and poorly defined Z-discs and display a reduction in sarcomere length as well as abnormal mitochondrial clumping under the sarcolemma. Furthermore, the dtTg4 skeletal muscles are weak and fragile. These skeletal muscle defects likely contribute to the limb incoordination phenotype displayed by these mice. Dystonin appears to play a more critical role in maintaining the stability of the cytoarchitecture in skeletal muscle fibers, rather than in the establishment of the cytoskeletal networks during muscle formation and Sildenafil development. This notion is further supported by primary myogenic cell culture experiments where it was shown that the Pranoprofen proliferation and differentiation potential of dtTg4 myogenic cells is similar to that of wild-type cells. Collectively, these findings support the idea that dystonin maintains the structural integrity of skeletal muscle cells although the precise cellular mechanisms by which it does so, has not been fully described. Dystonin is highly expressed in cardiac muscle and yet very little is known about the role of this molecule in heart tissue. Given the apparent function of dystonin in skeletal muscle cells, it is reasonable to expect that this crosslinking protein would have a key function in maintaining the structural integrity of cardiac tissue.