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Muscle Atrophy: Different Strains of Mice Respond Differently to Single Limb Immobilization
bioRxiv - Physiology Pub Date : 2020-11-04 , DOI: 10.1101/2020.11.03.367169
Camilla Reina Maroni , Michael A Friedman , Yue Zhang , Michael J McClure , Stefania Fulle , Charles R. Farber , Henry J. Donahue

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.

中文翻译:

肌肉萎缩:不同的小鼠应变对单肢固定反应不同。

为了检查遗传变异性是否在肌肉适应其机械环境中起作用,我们检查了五种不同小鼠品系的后肢固定化:CAST / EiJ,NOD / ShiLtJ,NZO / HILtJ,129S1 / SvImJ和A / J。小鼠的一只脚被石膏固定了三个星期。对固定的反应取决于所检查的小鼠的品系。A / J小鼠在固定后损失了最多的体重,并且表现出明显的体力活动下降。其他菌株均未显示出活性显着降低。NOD / ShiLtJ小鼠的食物消耗显着增加。所有其他菌株的食物消耗没有显着变化。除1291 / SvImJ外,所有菌株的肌肉质量/体重均因固定而降低。铸型降低了四头肌和腓肠肌的绝对肌肉质量,它们在两种可以发展成糖尿病的菌株——NOD / ShiltJ和NZO / HILtJ小鼠中都没有,而在其他菌株中却没有。固定三周后,CAST / EiJ小鼠的股四头肌的四头肌水平显着增加,而其他菌株则没有。固定化导致CAST / EiJ小鼠的股四头肌和腓肠肌Myh4水平显着增加,而其他任何菌株均没有。在腓肠肌中观察到Myh7的类似趋势。固定化导致NOD / ShiLtJ小鼠的股四头肌和A / J小鼠的腓肠肌的p-p70S6K1 /总p706SK1比率降低,而其他菌株则没有。固定化不影响任何所检查菌株的股四头肌中p-4EBP1 /总4EBP1的比例。然而,与对照相比,CAST / EiJ小鼠的固定肢体中腓肠肌的p-4EBP1 /总4EBP1比率更高。腓肠肌和股四头肌均按体重标准化的肌肉质量显示出最大的遗传力。这些结果揭示了跨越小鼠的五个不同遗传株对固定反应的显着差异。
更新日期:2020-11-06
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