Document Type
Article
Publication Date
6-1-2023
Original Citation
Oestereicher M,
Wotton J,
Ayabe S,
Bou About G,
Cheng T,
Choi J,
Clary D,
Dew E,
Elfertak L,
Guimond A,
Haseli Mashhadi H,
Heaney J,
Kelsey L,
Keskivali-Bond P,
Lopez Gomez F,
Marschall S,
McFarland M,
Meziane H,
Munoz Fuentes V,
Nam K,
Nichtová Z,
Pimm D,
Bower L,
Prochazka J,
Rozman J,
Santos L,
Stewart M,
Tanaka N,
Ward C,
Willett A,
Wilson R,
Braun R,
Dickinson M,
Flenniken A,
Herault Y,
Lloyd K,
Mallon A,
McKerlie C,
Murray SA,
Nutter L,
Sedlacek R,
Seong J,
Sorg T,
Tamura M,
Wells S,
Schneltzer E,
Fuchs H,
Gailus-Durner V,
Hrabe de Angelis M,
White J,
Spielmann N.
Comprehensive ECG reference intervals in C57BL/6N substrains provide a generalizable guide for cardiac electrophysiology studies in mice. Mamm Genome. 2023;34(2):180-99.
Keywords
JMG, Mice, Animals, Mice, Inbred C57BL, Electrophysiologic Techniques, Cardiac, Electrocardiography, Mice, Inbred Strains
JAX Source
Mamm Genome. 2023;34(2):180-99.
ISSN
1432-1777
PMID
37294348
DOI
https://doi.org/10.1007/s00335-023-09995-y
Grant
OpenAccessfundingenabledandorganizedbyProjektDEAL. The IMPC has been supported by National Institutes of Health (NIH) grants U54 HG006364, NIH U42 OD011175, NIH UM1 OD023221 (KCKL and CM); NIH UM1OD023222 (JW, SM, RB), MRC grant code MC_A410, NIH UM1HG006370 (TM, HP, PF, DS, JM, VM, HM); MRC funding for the IMPC ref 53658 (SW); Genome Canada and Ontario Genomics OGI-051(CM and SDMB); The Czech Centre for Phe- nogenomics is supported by RVO68378050 and projects LM2015040 LM2018126, CZ.1.05/1.1.00/02.0109, CZ.1.05/2.1.00/19.0395, CZ.0 2.1.01/0.0/0.0/16_013/0001789 and CZ.02.1.01/0.0/0.0/18_046/0015 861 (RS); the French Agence Nationale de la Recherche grants ANR- 10-IDEX-0002–02, ANR-10-LABX-0030-INRT, ANR-10-INBS-07 PHENOMIN (YH); European Union Horizon2020: IPAD-MD funding 653961 and the German Center for Diabetes Research (DZD), (MHA). National Key R& D program of China, 2018YFA0801100. This research was also partially supported by the R&D Project for the Korea Mouse Phenotyping Center (2013M3A9D5072550) of the National Research Foundation, which is funded by the Ministry of Science and ICT to Je Kyung Seong.
Abstract
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.
Comments
This article is licensed under a Creative Commons Attri- bution 4.0 International License, which permits use, sharing, adapta- tion, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicatedotherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.