Muscle Atrophy: Different Strains of Mice Respond Differently to Single Limb Immobilization

Abstract To examine whether genetic variability plays a role in muscle adaption to its mechanical environment, we examined hind limb immobilization in five different strains of mice: CAST/EiJ, NOD/ShiLtJ, NZO/HILtJ, 129S1/SvImJ and A/J. Mice had one limb immobilized by a cast for three weeks. The response to immobilization was dependent on the strain of mice examined. A/J mice lost the most body weight following immobilization and displayed a significant decrease in physical activity. None of the other strains displayed a significant decrease in activity. Food consumption was significantly increased in NOD/ShiLtJ mice. All other strains had non-significant changes in food consumption. Muscle mass/body weight was decreased by immobilization, to varying degrees, in all strains except 1291/SvImJ. Casting decreased absolute muscle mass in both quadriceps and gastrocnemius in NOD/ShiltJ and NZO/HILtJ mice, two strains that can develop diabetes, but not in the other strains. Three weeks of immobilization caused a significant increase in quadriceps levels of atrogenes in CAST/EiJ mice but not in other strains. Immobilization caused a significant increase in quadriceps and gastrocnemius levels of Myh4 in CAST/EiJ mice but not in any other strain. A similar trend was observed for Myh7 in gastrocnemius muscle. Immobilization resulted in a decrease the p-p70S6K1/total p706SK1 ratio in quadriceps of NOD/ShiLtJ mice and the gastrocnemius of A/J mice, but not in other strains. Immobilization did not affect the p-4EBP1/total 4EBP1 ratio in quadriceps of any of the strains examined. However, the p-4EBP1/total 4EBP1 ratio in gastrocnemius was greater in immobilized, relative to control, limbs in CAST/EiJ mice. Muscle mass normalized to body weight in both gastrocnemius and quadriceps displayed the greatest degree of heritability. These results reveal remarkable variability in responsiveness to immobilization across five different genetic strains of mice.