The Effects of Voluntary Wheel Running in Myhc-Iib Null Mice

To examine the plasticity of MyHC-IIb null skeletal muscle in response to endurance exercise, MyHC-IIb null mice were subjected to a voluntary wheel running paradigm. Voluntary wheel running in the non-transgenic C57/B6 mouse (NTG) results in a shift in MyHC isoform expression from the predominant MyHC-IIb towards the more oxidative MyHC-IIa isoform combined with hypertrophy of fibers expressing MyHC-IIa. Unexercised MyHC-IIb null mice exhibit increased MyHC-IId/x isoform expression along with increased muscle oxidative capacity via elevated levels of citrate synthase. In spite of compensation by the MyHC-IId/x gene, MyHC-IIb null mice exhibit a significant reduction in the mass of most hindlimb skeletal muscles combined with regions of muscle pathology. Male MyHC-IIb null mice 6 to 8 weeks of age were randomly divided into exercise (EX, n = 12) and non-exercise littermate controls (NE, n = 12). Ex animals were given access to a cage mounted free-wheel for periods of 1, 2, and 4 weeks. MyHC-IIb null mice ran an average of 5.17 ± 1.87 hours/night for an average distance of 5.93 ± 2.56 km/night (not significantly different from NTG). In contrast to the NTG response, immunohistochemical analysis of MyHC isoform composition in both the gastrocnemius (G) and tibialis anterior (TA) revealed no significant change in the percentage of fibers expressing MyHC-I,-IIa, or -IId with voluntary wheel running at any time point. A significant increase in the CSA of fibers expressing MyHC-IIa was observed in both G (1527 ± 341μm2 vs. 1394 ± 296μm2, p < 0.0001) and TA (2122 ± 695μm2 vs. 1725 ± 429μm2, p < 0.0001) with 4 weeks of wheel running as compared to NE control. We conclude that MyHC-IIb null mice show NTG levels of voluntary wheel running activity, and that this activity is sufficient to induce hypertrophy of fibers expressing MyHC-IIa. The lack of change in MyHC isoform expression may indicate that the fiber type profiles of these selected muscles, through compensatory changes in MyHC isoform gene expression and alterations in muscle enzymatic makeup, have sufficient oxidative capacity to deal with the stresses of unloaded voluntary wheel running.