Our results show that the primary cytoskeletal components, namely microfilaments, desmin intermediate filaments, and microtubules remain intact in dt hearts. Interestingly, dystonindeficient hearts do display features of hypertrophic cardiomyopathy at the molecular level but not at the morphological level. We have Pyriproxyfen generated an antibody to target the muscle isoform of dystonin. Our immunofluorescence data suggest that dystonin-b is localized at two specific sites in cardiac muscle fibers, namely at the Z-disc and within the H zone. The dystonin-b antibody produced a strong signal at Z-discs similar to desmin and aactinin. As compromised Z-disc ultrastructure has been previously reported in skeletal muscle from dt mice, it is possible that dystonin may play a role in assuring the structural integrity of Z-discs. At present, the role of dystonin-b at the Z-disc is not clear. Based on our immunofluorescence studies, it is unlikely that dystonin directly stabilizes desmin intermediate filaments at the Z-disc since the localization of desmin remains intact in dt hearts. A second striation detected with the dystonin-b antibody was parallel to the Z-disc and appeared to be present in the H-zone. Within this region, dystonin-b may further strengthen the sarcomere and protect it from contraction-induced stress along with other proteins such as titin. In addition, our findings demonstrate that dystonin-b is found at the sarcolemma and intercalated discs in mouse cardiac muscle. Intercalated discs are composed of other plakin family members such as plectin and desmoplakin. The requirement for multiple cytolinker proteins at this cardiac muscle adhesion structure likely reflects the greater need for structural support to resist the effects of chronic mechanical stress. Three N-terminal variants of dystonin-b isoforms, namely isoforms b1, b2 and b3 are expressed in cardiac tissue though their individual distribution in cardiac muscle fibers is not presently known. These unique N-terminal regions have been shown to direct dystonin Miglitol fusion proteins to distinct compartments within cells maintained in culture.