Tissue-Specific Cell Cycle Indicator Reveals Unexpected Findings for Cardiac Myocyte Proliferation

Rationale: Discerning cardiac myocyte cell cycle behavior is challenging owing to commingled cell types with higher proliferative activity. Objective: To investigate cardiac myocyte cell cycle activity in development and the early postnatal period. Methods and Results: To facilitate studies of cell type-specific proliferation, we have generated tissue-specific cell cycle indicator BAC transgenic mouse lines. Experiments using embryonic fibroblasts from CyclinA2-LacZ-floxed-EGFP, or CyclinA2-EGFP mice, demonstrated that CyclinA2-gal and CyclinA2-EGFP were expressed from mid-G1 to mid-M phase. Using Troponin T-Cre;CyclinA2-LacZ-EGFP mice, we examined cardiac myocyte cell cycle activity during embryogenesis and in the early postnatal period. Our data demonstrated that right ventricular cardiac myocytes exhibited reduced cell cycle activity relative to left ventricular cardiac myocytes in the immediate perinatal period. Additionally, in contrast to a recent report, we could find no evidence to support a burst of cardiac myocyte cell cycle activity at postnatal day 15. Conclusions: Our data highlight advantages of a cardiac myocyte-specific cell cycle reporter for studies of cardiac myocyte cell cycle regulation.