The CuraVita Corporation, Boston, MA, USA.
Altern Lab Anim. 2004 Jun;32 Suppl 1A:195-201. doi: 10.1177/026119290403201s33.
Linking gene defect to disease phenotypes in mice has become an essential step in the development of new drugs. Yet, many in vitro and in vivo assays require anaesthetic and surgery or do not reflect physiologically relevant phenomena. The effects of genes or diseases may only become apparent with stressors. Here, we apply non-invasive ECG monitoring and gait imaging systems to describe changes in the electrocardiogram and in gait dynamics resulting from a doubling of the ambulatory speed of mice. We found that B6C3H mice (n = 5) take 3.6 +/- 0.1 strides/second to walk 18cm/second and have a heart rate of 750 +/- 2bpm after 1 minute of walking at this speed. These mice significantly increase stride frequency to 5.2 +/- 0.1 strides/second in order to increase their speed to 36cm/second. The heart rate increased significantly (814 +/- 9bpm, p < 0.05) after trotting at the higher speed for 90 seconds, and the QRS interval duration significantly decreased (9.4 +/- 0.3ms vs. 10.4 +/- 0.3ms, p < 0.05). We discuss the application of the ECG screening and gait imaging systems to mouse models of Duchenne muscular dystrophy, Down syndrome and amyotrophic lateral sclerosis, diseases in humans that are known to affect the heart and neuromuscular systems.
将基因缺陷与小鼠疾病表型联系起来已成为开发新药的重要步骤。然而，许多体外和体内检测需要麻醉和手术，或者不能反映生理相关现象。基因或疾病的影响只有在应激源下才会显现出来。在这里，我们应用非侵入性心电图监测和步态成像系统来描述由于小鼠活动速度增加一倍而导致心电图和步态动力学的变化。我们发现 B6C3H 小鼠（n = 5）以 3.6 +/- 0.1 步/秒的速度行走 18cm/秒，在以该速度行走 1 分钟后心率为 750 +/- 2bpm。这些小鼠显著增加步频至 5.2 +/- 0.1 步/秒，以将速度提高到 36cm/秒。在以较高速度奔跑 90 秒后，心率显著增加（814 +/- 9bpm，p < 0.05），QRS 间隔持续时间显著缩短（9.4 +/- 0.3ms 对 10.4 +/- 0.3ms，p < 0.05）。我们讨论了心电图筛选和步态成像系统在人类疾病（已知影响心脏和神经肌肉系统的疾病）如杜氏肌营养不良症、唐氏综合征和肌萎缩侧索硬化症的小鼠模型中的应用。
