TY - JOUR
T1 - Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous cardiac remodeling
AU - da Costa Martins, Paula A.
AU - Bourajjaj, Meriem
AU - Gladka, Monika
AU - Kortland, Mara
AU - van Oort, Ralph J.
AU - Pinto, Yigal M.
AU - Molkentin, Jeffery D.
AU - de Windt, Leon J.
PY - 2008
Y1 - 2008
N2 - BACKGROUND: Dicer, an RNAse III endonuclease critical for processing of pre-microRNAs (miRNAs) into mature 22-nucleotide miRNAs, has proven a useful target to dissect the significance of miRNAs biogenesis in mammalian biology. METHODS AND RESULTS: To circumvent the embryonic lethality associated with germline null mutations for Dicer, we triggered conditional Dicer loss through the use of a tamoxifen-inducible Cre recombinase in the postnatal murine myocardium. Targeted Dicer deletion in 3-week-old mice provoked premature death within 1 week accompanied by mild ventricular remodeling and dramatic atrial enlargement. In the adult myocardium, loss of Dicer induced rapid and dramatic biventricular enlargement, accompanied by myocyte hypertrophy, myofiber disarray, ventricular fibrosis, and strong induction of fetal gene transcripts. Comparative miRNA profiling revealed a set of miRNAs that imply causality between miRNA depletion and spontaneous cardiac remodeling. CONCLUSIONS: Overall, these results indicate that modifications in miRNA biogenesis affect both juvenile and adult myocardial morphology and function
AB - BACKGROUND: Dicer, an RNAse III endonuclease critical for processing of pre-microRNAs (miRNAs) into mature 22-nucleotide miRNAs, has proven a useful target to dissect the significance of miRNAs biogenesis in mammalian biology. METHODS AND RESULTS: To circumvent the embryonic lethality associated with germline null mutations for Dicer, we triggered conditional Dicer loss through the use of a tamoxifen-inducible Cre recombinase in the postnatal murine myocardium. Targeted Dicer deletion in 3-week-old mice provoked premature death within 1 week accompanied by mild ventricular remodeling and dramatic atrial enlargement. In the adult myocardium, loss of Dicer induced rapid and dramatic biventricular enlargement, accompanied by myocyte hypertrophy, myofiber disarray, ventricular fibrosis, and strong induction of fetal gene transcripts. Comparative miRNA profiling revealed a set of miRNAs that imply causality between miRNA depletion and spontaneous cardiac remodeling. CONCLUSIONS: Overall, these results indicate that modifications in miRNA biogenesis affect both juvenile and adult myocardial morphology and function
U2 - https://doi.org/10.1161/CIRCULATIONAHA.108.769984
DO - https://doi.org/10.1161/CIRCULATIONAHA.108.769984
M3 - Article
C2 - 18809798
SN - 0009-7322
VL - 118
SP - 1567
EP - 1576
JO - Circulation
JF - Circulation
IS - 15
ER -