INTRODUCTION: Mouse models play a critical role in cardiology research, offering valuable insights into the molecular mechanisms, genetics, and potential treatments for cardiovascular diseases. However, the ability to transfer findings in mice between studies is limited by the absence of standardized protocols and valid reference values for the assessment of normal cardiac function in mice. This study aims to establish comprehensive transthoracic echocardiography (TTE) reference ranges for mice, particularly focusing on C57BL/6N wild-type controls. METHODS: The study, which includes data from over 15,000 mice through the International Mouse Phenotyping Consortium (IMPC), highlights how variables such as sex, age, body weight, and anesthesia impact TTE parameters. RESULTS: The findings showed that anesthesia is the primary predictor of variability in cardiac function. Isoflurane- and tribromoethanol-anesthetized mice presented with modified cardiac function compared with conscious mice. In addition, we observed minimal sex differences in cardiac morphology and function, except for small variations influenced by anesthesia. The effects of aging on cardiac function were modest, characterized by a decrease in heart rate and subtle changes in ventricular dimensions without evidence of pathological remodeling, possibly attributable to disease-free cardiovascular aging. DISCUSSION: Validation of the reference ranges across multiple mouse strains showed that these values provide a reliable baseline for experiments involving cardiac function in mice. The data underscore the importance of using anesthesia-specific reference values when interpreting TTE results, ensuring robust comparisons in genetic and pharmacological studies. These reference ranges serve as quality assurance tools for future cardiac studies in mice, offering insights into typical TTE parameter values, supporting the detection of experimental perturbations, and contributing to more effective translation of findings from mice to humans.

Advanced Technology Cores Baylor College of Medicine Houston TX United States

Chair of Experimental Genetics School of Life Science Weihenstephan Technische Universität München Freising Germany

Czech Centre for Phenogenomics Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

Department of Integrative Physiology Baylor College of Medicine Houston TX United States

Department of Molecular and Human Genetics Baylor College of Medicine Houston TX United States

European Molecular Biology Laboratory European Bioinformatics Institute Wellcome Trust Genome Campus Hinxton Cambridgeshire United Kingdom

German Center for Diabetes Research Neuherberg Germany

Institute of Experimental Genetics and German Mouse Clinic Helmholtz Center Munich German Research Center for Environmental Health Neuherberg Germany

SKL of Pharmaceutical Biotechnology and Model Animal Research Center Collaborative Innovation Center for Genetics and Development Nanjing Biomedical Research Institute Nanjing University Nanjing China

The Mary Lyon Centre and MRC Harwell Harwell Campus Oxfordshire United Kingdom

Université de Strasbourg CNRS INSERM Institute de la Clinique de la Souris PHENOMIN ILLKIRCH France

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