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.


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.
da Costa Martins
Paula A
PA
Department of Medical Physiology, University Medical Center Utrecht, Utrecht, Netherlands.
Bourajjaj
Meriem
M
Gladka
Monika
M
Kortland
Mara
M
van Oort
Ralph J
RJ
Pinto
Yigal M
YM
Molkentin
Jeffery D
JD
De Windt
Leon J
LJ
D000367:Age Factors; D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D016757:Death, Sudden, Cardiac; D004722:Endoribonucleases / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006333:Heart Failure / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D019426:Integrases / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D009206:Myocardium / Q000473:pathology*; D043244:Ribonuclease III; D012720:Severity of Illness Index; D020257:Ventricular Remodeling / Q000235:genetics*
D035683:MicroRNAs; C045073:Cre recombinase; D019426:Integrases; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases