High throughput phenotyping of left and right ventricular cardiomyopathy in calcineurin transgene mice

An Erratum to this article was published on 28 April 2015


Consistent protocols for the assessment of diastolic and systolic cardiac function to assure the comparability of existing data on preclinical models are missing. Calcineurin transgene (CN) mice are a preclinical model for hypertrophic and failing hearts. We aimed at evaluating left and right ventricular structural and functional remodeling in CN hearts with an optimized phenotyping protocol. We developed a protocol using techniques and indices comparable to those from human diagnostics for comprehensive in vivo cardiac screening using high-frequency echocardiography, Doppler, electrocardiography and cardiac magnetic resonance (CMR) techniques. We measured left and right ventricular dimensions and function, pulmonary and mitral flow pattern and the hearts electrophysiology non-invasively in <1 h per mouse. We found severe biventricular dilation and a drastic decline in performance in accordance with a condition of heart failure (HF), diastolic dysfunction and defects in electrical conduction in 8-week-old calcineurin transgenic mice. Echocardiography of the left ventricle was performed with and without anesthesia. In all cases absolute values on echocardiography compared with CMR were smaller for LV dimension and wall thickness, resulting in higher fractional shorting and ejection fraction. The study protocol described here opens opportunities to assess the added value of combined echocardiography, Doppler, CMR and ECG recording techniques for the diagnosis of biventricular cardiac pathologies i.e. of HF and to study symptom occurrence and disease progression non-invasively in high-throughput. Phenotyping CN hearts revealed new symptom occurrence and allowed insights into the diverse phenotype of hypertrophic failing hearts.

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We thank Ralf Fischer and Anna Nießer for data collection. The authors are grateful to the reviewers whose comments and suggestions significantly improved both clarity and precision of the paper. This study was supported by Grants from 01KX1012 Infrafrontier BMBF and Z56010017400 DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

All tests performed were approved by the responsible authority of the district government of Upper Bavaria, Germany.

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Correspondence to Kristin Moreth.

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Moreth, K., Afonso, L.C., Fuchs, H. et al. High throughput phenotyping of left and right ventricular cardiomyopathy in calcineurin transgene mice. Int J Cardiovasc Imaging 31, 669–679 (2015). https://doi.org/10.1007/s10554-015-0596-z

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  • Echocardiography
  • Magnetic resonance imaging
  • Electrocardiography
  • Doppler
  • Cardiac disease
  • Heart failure