Disease relevance of Myot

• Developmental expression of myotilin, a gene mutated in limb-girdle muscular dystrophy type 1A [1].
• In our effort towards the construction of a genetic model for myotilin-related muscle disorders, we have cloned mouse myotilin, including its promoter region, and studied the expression in various tissues [2].
• Targeted deletion of the muscular dystrophy gene myotilin does not perturb muscle structure or function in mice [3].

High impact information on Myot

• Missense mutations in the myotilin-encoding gene cause dominant limb girdle muscular dystrophy type 1A and spheroid body myopathy and are the molecular defect that can cause myofibrillar myopathy [3].
• The results suggest that either myotilin does not participate in muscle development and basal function maintenance or other proteins serve as structural and functional compensatory molecules when myotilin is absent [3].
• The direct binding to F-actin, efficient cross-linking of actin filaments, and prevention of induced disassembly of filaments are key roles of myotilin that are thought to be involved in structural maintenance and function of the sarcomere [3].
• Myotilin is a thin filament-associated protein localized at the Z-disk of skeletal and cardiac muscle cells [3].
• We have identified a C450T missense mutation in the myotilin gene that is predicted to result in the conversion of residue 57 from threonine to isoleucine [4].

Biological context of Myot

• Finally, endogenous myotilin is induced at later stages of Z-disc assembly in C(2)C(12) cells indicating conservation between mouse and human promoter region [2].
• Myotilin is expressed late during human myofibrillogenesis and localizes to Z-discs in mature sarcomere [2].

Anatomical context of Myot

• In situ hybridization and immunostaining of embryonic mouse tissues revealed expression of myotilin initially (E9-10) in heart, somites and neuroepithelium [1].
• These features suggest an important role for myotilin in sarcomere organization [2].

References