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TY - JOUR AU - Oestereicher, Manuela A. AU - Wotton, Janine M. AU - Ayabe, Shinya AU - Bou About, Ghina AU - Cheng, Tsz Kwan AU - Choi, Jae-Hoon AU - Clary, Dave AU - Dew, Emily M. AU - Elfertak, Lahcen AU - Guimond, Alain AU - Haseli Mashhadi, Hamed AU - Heaney, Jason D. AU - Kelsey, Lois AU - Keskivali-Bond, Piia AU - Lopez Gomez, Federico AU - Marschall, Susan AU - McFarland, Michael AU - Meziane , Hamid AU - Munoz Fuentes, Violeta AU - Nam , Ki-Hoan AU - Nichtová, Zuzana AU - Pimm, Dale AU - Bower, Lynette AU - Prochazka, Jan AU - Rozman, Jan AU - Santos, Luis AU - Stewart, Michelle AU - Tanaka, Nobuhiko AU - Ward, Christopher S. AU - Willett, Amelia M. E. AU - Wilson, Robert AU - Braun, Robert E. AU - Dickinson, Mary E. AU - Flenniken, Ann M. AU - Herault, Yann AU - Lloyd, K. C. Kent AU - Mallon, Ann-Marie AU - McKerlie, Colin AU - Murray, Stephen A. AU - Nutter, Lauryl M. J. AU - Sedlacek, Radislav AU - Seong, Je Kyung AU - Sorg, Tania AU - Tamura, Masaru AU - Wells, Sara AU - Schneltzer, Elida AU - Fuchs, Helmut AU - Gailus-Durner, Valerie AU - Hrabe de Angelis, Martin AU - White, Jacqueline K. AU - Spielmann, Nadine PY - 2023 DA - 2023/06/01 TI - Comprehensive ECG reference intervals in C57BL/6N substrains provide a generalizable guide for cardiac electrophysiology studies in mice JO - Mammalian Genome SP - 180 EP - 199 VL - 34 IS - 2 AB - 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. SN - 1432-1777 UR - https://doi.org/10.1007/s00335-023-09995-y DO - 10.1007/s00335-023-09995-y ID - Oestereicher2023 ER -