Myostatin dysfunction is associated with reduction in overload induced hypertrophy of soleus muscle in mice.

The aim of the study was to investigate if myostatin dysfunction would promote the gain in muscle mass and peak isometric force (P0 ) of soleus muscle (SOL) in response to functional overloading (FO) after ablation of the gastrocnemius muscle. Fifteen male Berlin high (BEH) mice homozygous for the compact mutation causing dysfunction of myostatin and 17 mice with the corresponding wild-type allele (BEH+/+) were subjected to FO of SOL for 28 days at the age of 14 weeks. Compared with BEH+/+ mice, SOL of BEH was heavier (mean ± SD, 13.5 ± 1.5 vs 21.4 ± 1.8 mg, respectively, P < 0.001). After FO, SOL mass increased relatively more in BEH+/+ than BEH strain (34.9 ± 11.5 vs 17.7 ± 11.9%, respectively, P < 0.01). P0 fell (P < 0.01) only in BEH strain, which also showed an increase (P < 0.01) in optimal muscle length. Specific P0 became even more depressed in BEH compared with BEH+/+ strain (8.4 ± 1.4 vs 10.8 ± 1.3 N/g, respectively, P < 0.001). Phosphorylation p70 S6 kinase did not differ between the strains. In summary, myostatin dysfunction impairs adaptation of SOL muscle to high functional demands.

Divergent physiological characteristics and responses to endurance training among inbred mouse strains.

Both baseline values and adaptive changes in mice can vary depending on the genetic background. We aimed to assess variation in a battery of variables and their adaptations to endurance training in six inbred mouse strains. Males, n = 184, from A/J, BALB/cByJ, C3H/HeJ, C57BL/6J, DBA/2J, and PWD/PhJ strains were assigned to a control or an endurance group (5 weeks swimming exercise). Enzyme activity, histology of soleus (SOL) muscle, swimming endurance, cardiac ventricular and hind limb muscle weight, and femur length were examined. Endurance capacity, morphological and histological variables, and enzyme activity substantially differed among strains. For example, SOL weight was twofold higher and cross-sectional area (CSA) of fibers was ≈ 30% greater in C57BL/6J than in PWD/PhJ strain. The CSA of type 1 fibers were larger than type 2A in PWD/PhJ (P < 0.01); however, the reverse was true in DBA/2J and BALB/cByJ strains (P < 0.05). Swimming endurance in DBA/2J strain was ≈ 9 times better than in BALB/cByJ. Endurance training increased the activity of citrate synthase in gastrocnemius across strains (P < 0.01), however, changes in endurance were strain-specific; the C57BL/6J and DBA/2J strains improved substantially, whereas A/J and BALB/cByJ strains did not. In conclusion, genetic background is a potent determinant of the physiological characteristics and adaptations to training in mice.