Key result
Postnatal cardiac Dicer deletion triggers rapid biventricular enlargement and premature death within ~1 week.
Why the study?
Germline null mutations for Dicer cause embryonic lethality, motivating conditional deletion in the postnatal murine myocardium to dissect the significance of microRNA biogenesis.
Does conditional Dicer gene deletion provoke spontaneous cardiac remodeling in postnatal mice?
Does conditional Dicer gene deletion provoke spontaneous cardiac remodeling in postnatal mice?
Conditional deletion of Dicer in the postnatal murine myocardium demonstrates that miRNA biogenesis is essential for maintaining normal cardiac morphology and function, as its loss leads to rapid cardiac remodeling and death.
Hypothesis-generating for miRNA biogenesis in cardiac homeostasis; leaves open therapeutic relevance in human 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.
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Martins et al. (2008) studied Cardiac remodeling. Conditional Dicer gene deletion was evaluated on Myocardial morphology and function (survival and cardiac remodeling). Conditional Dicer gene deletion in the postnatal murine myocardium provoked premature death within 1 week in 3-week-old mice and rapid biventricular enlargement in adult mice.
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