Conditional Dicer Gene Deletion in the Postnatal Myocardium Provokes Spontaneous Cardiac Remodeling
Copyright policy )Conditional Dicer Gene Deletion in the Postnatal Myocardium Provokes Spontaneous Cardiac Remodeling
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.
- Amsterdam UMC Netherlands
- Utrecht University Netherlands
- Royal Netherlands Academy of Arts and Sciences Netherlands
- Hubrecht Institute for Developmental Biology and Stem Cell Research Netherlands
- University Medical Center Utrecht Netherlands
Heart Failure, Male, Ribonuclease III, Integrases, Ventricular Remodeling, Myocardium, Age Factors, Gene Expression Regulation, Developmental, Cardiomegaly, Mice, Transgenic, Severity of Illness Index, DEAD-box RNA Helicases, Mice, MicroRNAs, Death, Sudden, Cardiac, Endoribonucleases, Animals, Female, Gene Deletion
Heart Failure, Male, Ribonuclease III, Integrases, Ventricular Remodeling, Myocardium, Age Factors, Gene Expression Regulation, Developmental, Cardiomegaly, Mice, Transgenic, Severity of Illness Index, DEAD-box RNA Helicases, Mice, MicroRNAs, Death, Sudden, Cardiac, Endoribonucleases, Animals, Female, Gene Deletion
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).266 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!