Desmin is a muscle-specific intermediate filament, which maintains muscle structural integrity and helps transmit force through cells. Without desmin, myofibrils are disorganized, nuclei are de-coupled from the cellular cytoskeleton, muscle force generation is lower and muscles are injured less than wild-type controls (Shah et al., 2003, Sam et al., 2000). To determine whether these changes are due to the absence of desmin directly or are secondary effects of development in the absence of desmin, desmin-null muscles were transfected with GFP-desmin plasmids. Measurements of Z-disk stagger in GFP-desmin transfected muscle fibers showed rescued alignment of myofibrils. Also, exogenous desmin provided functional connections to nuclei as seen by increased nuclear aspect ratio during deformation in transfected fibers vs. desmin-null controls. Cell signaling, in response to passive stretch, was increased in GFP-desmin transfected muscles as seen by upregulated JNK phosphorylation compared to desmin-null controls suggesting restored mechanotransduction. Nuclear connections established in transfected fibers allowed for increased cellular signaling, which may lead to gene modification. Functional testing revealed an increase in injury in GFP-desmin transfected muscles that was dependent on the amount of exogenous desmin expressed. Transfection of desmin in muscle not only restored desmin content, but also incorporated protein into the myofibrillar lattice that was functionally relevant. These studies showed that desmin is directly responsible for the alignment of myofibrils and is important for nuclear positioning, nuclear deformation, cell signaling and transmission of force.

There are no human muscle tissues that do not contain desmin however, there are over twenty mutations in the human desmin gene reported to date that cause muscle myopathies. These diseases result in abnormal accumulation of desmin in cells and interference with normal muscle structure and function. One such desmin mutation, L345P, was created and transfected into muscle in order to investigate the effects of mutated desmin in skeletal muscle. This provides an approach to understanding how mutated desmin behaves in vivo and gives insight into therapies to stop or slow down the progression of disease due to desminopathies.