A review of standardized high-throughput cardiovascular phenotyping with a link to metabolism in mice

Cardiovascular diseases cause a high mortality rate worldwide and represent a major burden for health care systems. Experimental rodent models play a central role in cardiovascular disease research by effectively simulating human cardiovascular diseases. Using mice, the International Mouse Phenotyping Consortium (IMPC) aims to target each protein-coding gene and phenotype multiple organ systems in single-gene knockout models by a global network of mouse clinics. In this review, we summarize the current advances of the IMPC in cardiac research and describe in detail the diagnostic requirements of high-throughput electrocardiography and transthoracic echocardiography capable of detecting cardiac arrhythmias and cardiomyopathies in mice. Beyond that, we are linking metabolism to the heart and describing phenotypes that emerge in a set of known genes, when knocked out in mice, such as the leptin receptor (Lepr), leptin (Lep), and Bardet-Biedl syndrome 5 (Bbs5). Furthermore, we are presenting not yet associated loss-of-function genes affecting both, metabolism and the cardiovascular system, such as the RING finger protein 10 (Rfn10), F-box protein 38 (Fbxo38), and Dipeptidyl peptidase 8 (Dpp8). These extensive high-throughput data from IMPC mice provide a promising opportunity to explore genetics causing metabolic heart disease with an important translational approach.

Automated summary

Cardiovascular diseases have a high mortality rate globally and pose a significant burden on health care systems. The International Mouse Phenotyping Consortium (IMPC) utilizes mouse models to study cardiovascular diseases and aims to target each protein-coding gene to examine multiple organ systems. This review discusses the recent advances of the IMPC in cardiac research, focusing on the diagnostic requirements for high-throughput electrocardiography and transthoracic echocardiography in mice. Additionally, it explores the relationship between metabolism and the heart, highlighting the phenotypes that emerge in knockout mice for certain genes and identifying novel loss-of-function genes affecting both metabolism and the cardiovascular system.