Maintenance of muscle mass, fiber size, and contractile function in mice lacking the Z-disc protein myotilin

Abstract

Background. Myofibrillar myopathies constitute a rare group of congenital neuromuscular disorders, frequently associated with mutations in Z-disc proteins such as myotilin. Myotilin location and interactions with other Z-disc proteins are clearly defined, but its role in the regulation of muscle structure and function remains unknown. The present study aims at investigating this specific role of myotilin.

Methods. Skeletal and cardiac muscles were collected from adult mice with a targeted deletion of myotilin (myo^-/-) and wild-type animals (myo^+/+).

Results and conclusion. Similar skeletal and cardiac muscle weights were observed in myo^-/- and myo^+/+ mice. At the muscle cell level, the size and force production of single membrane permeabilized fibers were identical between myo^-/- and myo^+/+ rodents. Thus, myotilin does not have a significant influence on muscle mass, muscle fiber size, or regulation of muscle contraction. Alternatively, compensatory over-expressions of other elements including proteins from the same subfamily, or Z-disc proteins such as telethonin, or intermediate filaments may compensate for the lack of myotilin.

Key words::

• Muscle
• myotilin
• single membrane permeabilized muscle fiber
• telethonin

Acknowledgements

We are grateful to Yvette Hedström and Ann-Marie Gustafsson for excellent technical assistance. This study was supported by grants from the Association Française contre les Myopathies, Tore Nilsons Stiftelsen för Medicinsk Forskning, Stiftelsen Apotekare Hedbergs Fond för Medicinsk Forskning, and the Swedish Research Council (8651). The authors have no conflicts of interest.