Abstract
Although amphibian and fish models of heart regeneration have existed for decades, a mammalian equivalent has long remained elusive. Our discovery of a brief postnatal window for heart regeneration in neonatal mice has led to the establishment of surgical models for cardiac regenerative studies in mammals for the first time. This protocol describes a 10-min surgical procedure to induce cardiac injury in 1-d-old neonatal mice. This allows for the analysis of cardiac regeneration after surgical amputation of the left ventricle (LV) (apical resection) and coronary artery occlusion (myocardial infarction (MI)). A comparative analysis of neonatal and adult responses to myocardial injury should enable identification of the key differences between regenerative and nonregenerative responses to cardiac injury. This protocol can also be adapted to the growing repertoire of genetic models available in the mouse, and it provides a valuable tool for unlocking the molecular mechanisms that guide mammalian heart regeneration during early postnatal life.
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Acknowledgements
We thank J. Cabrera for graphical assistance. This work was supported by the National Health and Medical Research Council and National Heart Foundation of Australia (E.R.P.), a cardiovascular research scholar award from Gilead Sciences, a Grant-in-Aid award from the American Heart Association and an NIH R01 grant (1R01HL115275-01; H.A.S.).
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A.I.M., E.R.P., E.N.O. and H.A.S. designed the experiments. A.I.M. and E.R.P. performed the experiments. A.I.M., E.R.P., E.N.O. and H.A.S. analyzed the data. A.I.M., W.K. and H.A.S. made the figures. A.I.M., E.R.P. and H.A.S. wrote the manuscript. All authors approved the manuscript.
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Mahmoud, A., Porrello, E., Kimura, W. et al. Surgical models for cardiac regeneration in neonatal mice. Nat Protoc 9, 305–311 (2014). https://doi.org/10.1038/nprot.2014.021
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DOI: https://doi.org/10.1038/nprot.2014.021
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