. 2014 Jul 22;3(3):724–750. doi: 10.3390/cells3030724

Table 1.

miRNA mutations and corresponding cardiac phenotypes.

miRNA	Organism	Mutation	Phenotype	Citation
Dicer1 (ribonuclease required for processing pre-miRNAs to maturity)	Zebrafish	Null	Growth arrest; death by 13–14 d.p.f	[43]
	Mouse	Null	Lethal (E7.5)	[42]
		CKO: Nkx2.5-Cre; Dicer^Fl/Fl	Lethal (E12.5): myocardial abnormalities, pericardial edema	[44]
		CKO: Nkx2.5-Cre (3'UTR-IRES-Cre); Dicer^Fl/Fl	Lethal (E13.5): VSD, DORV, reduced OFT apoptosis	[45]
		CKO: Wnt1-Cre; Dicer^Fl/Fl	Loss of sympathetic neurons; morphological defects (type B interrupted aortic arch, VSD, DORV, retroesophageal right subclavian artery, ectopic carotids)	[46,47]
		CKO: αMHC-Cre; Dicer^Fl/Fl	Dilative cardiomyopathy and heart failure; death by P4	[48]
		CKO: αMHC-MCM; Dicer^Fl/Fl (3-weeks old)	Spontaneous cardiac remodeling (mild RV inflammation, atrial enlargement); sudden death by 4 weeks of age	[49]
		CKO: αMHC-MCM; Dicer^Fl/Fl (adult)	Ventricular enlargement; cardiomyocyte hypertrophy and disarray; severe inflammation; interstitial ventricular fibrosis	[49]
Dgcr8 (Cofactor required for cleavage of pri-miRNA hairpins)	Mouse	CKO: Wnt1-Cre; Dgcr8^Fl/Fl	Persistent truncus arteriosis; VSD; interrupted aortic arch; cervical aortic arch; aberrant origin of right subclavian artery	[50]
	Mouse	CKO: MCK-Cre; Dgcr8^Fl/Fl	Reduced myocardial wall thickness; disrupted cardiac conduction; dilative cardiomyopathy; death by 2 months of age	[51]
miR-1-1	Mouse	Null: pGK-neomycin retained	Incompletely penetrant lethality (Sv129 background); ventricular dilation; conduction defects	[52]
miR-1-2	Mouse	Null: lacZ-pGK-neomycin retained	Incompletely penetrant lethality (E15.5-birth): VSD; cardiac dilation; atrial thrombosis; CM hyperplasia; conduction defects	[44]
miR-1	Drosophila	Null	Lethal (larval stages): Body wall collapse; striated muscle patterning defects	[53,54]
	Mouse	Null: neomycin-resistance cassettes retained	Lethal (P10): VSD, aortal misalignment; cardiac dilation; sarcomere disruption and retention of fetal sarcomere gene expression program	[52]
	Mouse	Null: neomycin-resistance cassettes excised	Lethal (P17): Dilative cardiomyopathy, CM hyperplasia; retention of fetal sarcomere gene expression program	[55]
miR-133a	Mouse	Null	Incompletely penetrant lethality (P1): VSD; increased CM proliferation and ectopic smooth muscle gene expression	[56]
miR-1/133	Zebrafish	MO-miR-1/133	Disrupted sarcomeric actin organization (loss of I-bands)	[57]
miR-1/133	Mouse	Null	Lethal (E11.5): Impaired circulation, upregulation of smooth muscle gene expression	[58]
miR-138	Zebrafish	MO-miR-138	Retention of immature CM morphology; ectopic expression of genes restricted to AVC	[59]
miR-218	Zebrafish	MO-miR-218	Impaired migration of heart field progenitors; severe pericardial edema; morphological defects; ectopic expression of endothelial markers	[60,61]
miR-92	Zebrafish	miR-92 mimic	Cardia bifida	[62]
miR-92	Zebrafish	MO-miR-92	Left-right asymmetry defects	[62]
miR-195	Mouse	βMHC-miR-195 transgenic	Reduced CM proliferation; VSD; ventricular hypoplasia; dilative cardiomyopathy; premature death	[63]
miR-17	Mouse	miR-17 transgenic	Reduced heart weight	[64]
miR-17~92	Mouse	Null	Perinatally lethal: VSD	[65]
miR-17~92	Mouse	SM22α-Cre; miR-17~92 transgenic	Cardiac hyperplasia and hypertrophy; sudden death by 2 months of age	[65]
miR-17~92; miR-106b~25	Mouse	Null	Embryonic lethal (E15): Ventricular hypoplasia, ASD, VSD, vascular congestion, edema	[66]
miR-208a	Mouse	Null	Sarcomere structural abnormalities, arrhythmias, ectopic expression of skeletal muscle genes	[67,68]

Abbreviations: ASD: atrial septal defect; AVC: atrioventricular canal; CM: cardiomyocyte; CKO: conditional knock-out; d.p.f.: days post-fertilization; DORV: double-outlet right ventricle; Fl/Fl: Homozygous floxed allele; MCM: Mer-Cre-Mer; MO: morpholino; OFT: outflow tract; RV: right ventricle; VSD: ventricular septal defect.