Institute of Experimental Genetics and German Mouse Clinic, Helmholtz Center Munich, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA.
Mamm Genome. 2023 Jun;34(2):180-199. doi: 10.1007/s00335-023-09995-y. Epub 2023 Jun 9.
Reference ranges provide a powerful tool for diagnostic decision-making in clinical medicine and are enormously valuable for understanding normality in pre-clinical scientific research that uses in vivo models. As yet, there are no published reference ranges for electrocardiography (ECG) in the laboratory mouse. The first mouse-specific reference ranges for the assessment of electrical conduction are reported herein generated from an ECG dataset of unprecedented scale. International Mouse Phenotyping Consortium data from over 26,000 conscious or anesthetized C57BL/6N wildtype control mice were stratified by sex and age to develop robust ECG reference ranges. Interesting findings include that heart rate and key elements from the ECG waveform (RR-, PR-, ST-, QT-interval, QT corrected, and QRS complex) demonstrate minimal sexual dimorphism. As expected, anesthesia induces a decrease in heart rate and was shown for both inhalation (isoflurane) and injectable (tribromoethanol) anesthesia. In the absence of pharmacological, environmental, or genetic challenges, we did not observe major age-related ECG changes in C57BL/6N-inbred mice as the differences in the reference ranges of 12-week-old compared to 62-week-old mice were negligible. The generalizability of the C57BL/6N substrain reference ranges was demonstrated by comparison with ECG data from a wide range of non-IMPC studies. The close overlap in data from a wide range of mouse strains suggests that the C57BL/6N-based reference ranges can be used as a robust and comprehensive indicator of normality. We report a unique ECG reference resource of fundamental importance for any experimental study of cardiac function in mice.
参考范围为临床医学中的诊断决策提供了强有力的工具，对于理解使用体内模型的临床前科学研究中的正常情况也具有巨大价值。然而，目前还没有实验室小鼠心电图（ECG）的参考范围。本文报告了首个专门用于评估电传导的鼠标特异性参考范围，这些参考范围是根据前所未有的 ECG 数据集生成的。国际小鼠表型分析联盟的数据来自超过 26000 只清醒或麻醉的 C57BL/6N 野生型对照小鼠，按性别和年龄分层，以制定稳健的 ECG 参考范围。有趣的发现包括心率和 ECG 波形的关键元素（RR-、PR-、ST-、QT 间期、QT 校正和 QRS 复合波）表现出最小的性别二态性。正如预期的那样，麻醉会降低心率，吸入麻醉（异氟烷）和注射麻醉（三溴乙醇）都有这种情况。在没有药理、环境或遗传挑战的情况下，我们没有观察到 C57BL/6N 近交系小鼠的主要年龄相关 ECG 变化，因为 12 周龄和 62 周龄小鼠的参考范围差异可以忽略不计。通过与来自广泛非 IMPC 研究的 ECG 数据进行比较，证明了 C57BL/6N 亚系参考范围的通用性。来自广泛小鼠品系的数据的紧密重叠表明，基于 C57BL/6N 的参考范围可作为心脏功能实验研究中正常情况的可靠且全面的指标。我们报告了一个独特的 ECG 参考资源，对于任何在小鼠中进行心脏功能的实验研究都具有重要意义。
