Developments in long-term space exploration necessitate advancements in countermeasures against microgravity-induced skeletal muscle loss. Astronaut data shows considerable variation in muscle loss in response to microgravity. Previous experiments suggest that genetic background influences the skeletal muscle response to unloading, but no in-depth analysis of genetic expression has been performed. Here, we placed eight, male, inbred founder strains of the diversity outbred mice (129S1/SvImJ, A/J, C57BL/6J, CAST/EiJ, NOD/ShiLtJ, NZO/HILtJ, PWK/PhJ, and WSB/EiJ) in simulated microgravity (SM) via hindlimb unloading for three weeks. Body weight, muscle morphology, muscle strength, protein synthesis marker expression, and RNA expression were collected. A/J and CAST/EiJ mice were most susceptible to SM-induced muscle loss, whereas NOD/ShiLtJ mice were the most protected. In response to SM, A/J and CAST/EiJ mice experienced reductions in body weight, muscle mass, muscle volume, and muscle cross-sectional area. A/J mice had the highest number of differentially expressed genes (68) and associated gene ontologies (328). Downregulation of immunological gene ontologies and genes encoding anabolic immune factors suggest that immune dysregulation contributes to the response of A/J mice to SM. Several muscle properties showed significant interactions between SM and mouse strain and a high degree of heritability. These data imply that genetic background plays a role in the degree of muscle loss in SM and that more individualized programs should be developed for astronauts to protect their skeletal muscles against microgravity on long-term missions.

长期太空探索的发展需要针对微重力引起的骨骼肌损失采取对策。宇航员数据显示，微重力引起的肌肉损失有相当大的变化。先前的实验表明，遗传背景影响骨骼肌对卸载的反应，但尚未对遗传表达进行深入分析。在这里，我们放置了八种雄性近交创始人品系的多样性远交小鼠（129S1/SvImJ、A/J、C57BL/6J、CAST/EiJ、NOD/ShiLtJ、NZO/HILtJ、PWK/PhJ 和 WSB/EiJ）通过后肢卸载在模拟微重力（SM）中持续三周。收集体重、肌肉形态、肌肉力量、蛋白质合成标志物表达和RNA表达。A/J 和 CAST/EiJ 小鼠最容易受到 SM 诱导的肌肉损失的影响，而 NOD/ShiLtJ 小鼠受到的保护最明显。作为对 SM 的反应，A/J 和 CAST/EiJ 小鼠的体重、肌肉质量、肌肉体积和肌肉横截面积均出现减少。A/J 小鼠具有最多数量的差异表达基因 (68) 和相关基因本体 (328)。免疫基因本体和编码合成代谢免疫因子的基因的下调表明免疫失调有助于 A/J 小鼠对 SM 的反应。一些肌肉特性显示 SM 和小鼠品系之间存在显着的相互作用以及高度的遗传性。这些数据表明，遗传背景在 SM 的肌肉损失程度中发挥着重要作用，并且应该为宇航员制定更个性化的计划，以保护他们的骨骼肌在长期任务中免受微重力的影响。