Key result
PostnMCM specifically tracks activated cardiac fibroblasts without endothelial leakage, outperforming alternative Cre lines.
Why the study?
There is no consensus on the ideal Cre recombinase transgenic mouse model to optimally identify and regulate cardiac fibroblasts.
Which inducible Cre mouse model provides the most efficient and specific tracking of cardiac fibroblasts in healthy and infarcted myocardium?
Which inducible Cre mouse model provides the most efficient and specific tracking of cardiac fibroblasts in healthy and infarcted myocardium?
The PostnMCM mouse line is the most reliable model for specific in vivo tracking of activated cardiac fibroblasts in cardiovascular disease studies.
PostnMCM enables specific fibroblast tracking in mouse MI models; leaves open translation to human cardiovascular research.
Several Cre recombinase transgenic mouse models have been generated for cardiac fibroblast (CF) tracking and heart regulation. However, there is still no consensus on the ideal mouse model to optimally identify and/or regulate these cells. Here, a comparative evaluation of the efficiency and specificity of the indirect reporter Cre-loxP system was carried out in three of the most commonly used fibroblast reporter transgenic mice (Pdgfra-CreERT2, Col1a1-CreERT2 and PostnMCM) under healthy and ischemic conditions, to determine their suitability in in vivo studies of cardiac fibrosis. We demonstrate optimal Cre recombinase activity in CF (but also, although moderate, in endothelial cells (ECs)) derived from healthy and infarcted hearts in the PDGFRa-creERT2 mouse strain. In contrast, no positive reporter signal was found in CF derived from the Col1a1-CreERT2 mice. Finally, in the PostnMCM line, fluorescent reporter expression was specifically detected in activated CF but not in EC, which leads us to conclude that it may be the most reliable model for future studies on cardiovascular disease. Importantly, no lethality or cardiac fibrosis were induced after tamoxifen administration at the established doses, either in healthy or infarcted mice of the three fibroblast reporter lineages. This study lays the groundwork for future efficient in vivo CF tracking and functional analyses.
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Aguado‐Alvaro et al. (2022) studied Cardiac Fibrosis and Myocardial Infarction. Fibroblast reporter transgenic mouse models (Pdgfra-CreERT2, Col1a1-CreERT2, PostnMCM) induced by tamoxifen vs. Cre-negative mice was evaluated on Efficiency and specificity of Cre recombinase activity in cardiac fibroblasts (reporter protein expression). The PostnMCM mouse model specifically tracked activated cardiac fibroblasts without endothelial leakage, whereas Pdgfra-CreERT2 labeled endothelial cells and Col1a1-CreERT2 showed no reporter signal.
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