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Updated: Aug 9, 2025
Isolation and Physiological Analysis of Mouse Cardiomyocytes
Published on: September 7, 2014
Cardiac copper content and its relationship with heart physiology: Insights based on quantitative genetic and
Akhilesh Kumar Bajpai1, Qingqing Gu1,2, Buyan-Ochir Orgil3,4
1Department of Genetics, Genomics and Informatics, The University of Tennessee Health Science Center, Memphis, TN, United States.
Insights
Copper levels in the heart impact cardiac size and thickness. Genetic mapping in BXD mice identified key genes, Prex1 and Irx3, influencing copper metabolism and heart traits.
Area of Science:
- Cardiovascular Biology
- Genetics
- Trace Element Metabolism
Background:
- Copper (Cu) is vital for cardiac function, but imbalances can cause heart disease.
- The genetic underpinnings of cardiac copper levels and their impact on heart traits are not fully understood.
- The BXD mouse strain resource is valuable for genetic association studies.
Purpose of the Study:
- To investigate the genetic basis of cardiac copper concentration in mice.
- To identify quantitative trait loci (QTLs) and candidate genes influencing heart copper levels.
- To explore the relationship between cardiac copper and heart morphology.
Main Methods:
- Cardiac copper concentration and heart function were measured in BXD mice.
- Quantitative trait locus (QTL) mapping was performed to identify genetic loci.
- A multi-criteria approach was used to identify candidate genes modulating copper homeostasis.
Main Results:
- Cardiac copper concentration correlated with left ventricular (LV) diameter and volume.
- Higher cardiac copper was linked to larger LV chamber size.
- Lower cardiac copper was associated with LV hypertrophy (thicker walls).
- Six QTLs were identified, containing 217 genes, narrowed to 21 significant candidates.
- Prex1 and Irx3 emerged as strong candidates for cardiac copper modulation.
Conclusions:
- Cardiac copper levels are significantly associated with heart chamber size and hypertrophy in BXD mice.
- Multiple genes within several QTLs regulate cardiac copper.
- Prex1 and Irx3 are potential key players in modulating copper metabolism and its cardiac effects, requiring further validation.
Background:
Copper (Cu) is essential for the functioning of various enzymes involved in important cellular and physiological processes. Although critical for normal cardiac function, excessive accumulation, or deficiency of Cu in the myocardium is detrimental to the heart. Fluctuations in cardiac Cu content have been shown to cause cardiac pathologies and imbalance in systemic Cu metabolism. However, the genetic basis underlying cardiac Cu levels and their effects on heart traits remain to be understood. Representing the largest murine genetic reference population, BXD strains have been widely used to explore genotype-phenotype associations and identify quantitative trait loci (QTL) and candidate genes.
Methods:
Cardiac Cu concentration and heart function in BXD strains were measured, followed by QTL mapping. The candidate genes modulating Cu homeostasis in mice hearts were identified using a multi-criteria scoring/filtering approach.
Results:
Significant correlations were identified between cardiac Cu concentration and left ventricular (LV) internal diameter and volumes at end-diastole and end-systole, demonstrating that the BXDs with higher cardiac Cu levels have larger LV chamber. Conversely, cardiac Cu levels negatively correlated with LV posterior wall thickness, suggesting that lower Cu concentration in the heart is associated with LV hypertrophy. Genetic mapping identified six QTLs containing a total of 217 genes, which were further narrowed down to 21 genes that showed a significant association with cardiac Cu content in mice. Among those, Prex1 and Irx3 are the strongest candidates involved in cardiac Cu modulation.
Conclusion:
Cardiac Cu level is significantly correlated with heart chamber size and hypertrophy phenotypes in BXD mice, while being regulated by multiple genes in several QTLs. Prex1 and Irx3 may be involved in modulating Cu metabolism and its downstream effects and warrant further experimental and functional validations.
