Desmin knockout muscles generate lower stress and are less vulnerable to injury compared with wild-type muscles.

The functional role of the skeletal muscle intermediate filament system was investigated by measuring the magnitude of muscle force loss after cyclic eccentric contraction (EC) in normal and desmin null mouse extensor digitorum longus muscles. Isometric stress generated was significantly greater in wild-type (313 +/- 8 kPa) compared with knockout muscles (276 +/- 13 kPa) before EC (P < 0.05), but 1 h after 10 ECs, both muscle types generated identical levels of stress ( approximately 250 kPa), suggesting less injury to the knockout. Differences in injury susceptibility were not explained by the different absolute stress levels imposed on wild-type versus knockout muscles (determined by testing older muscles) or by differences in fiber length or mechanical energy absorbed. Morphometric analysis of longitudinal electron micrographs indicated that Z disks from knockout muscles were more staggered (0.36 +/- 0. 03 microm) compared with wild-type muscles (0.22 +/- 0.03 microm), which may indicate that the knockout cytoskeleton is more compliant. These data demonstrate that lack of the intermediate filament system decreases isometric stress production and that the desmin knockout muscle is less vulnerable to mechanical injury.