Table 2. Mouse knockout phenotype for non-redundant miRNAs.

A summary of the phenotypes observed for mouse knockout studies to date examining miRNAs that have no known redundancy. Dark pink, polycistronic miRNAs; light pink, moncistronic miRNAs.

miRNA family		Phenotypic characterization	Comments	References
Polycistronic miRNAs	miR-143/145	miR-143/145−/− mice are viable, but exhibit a variety of smooth muscle defects. Vascular smooth muscle cells are reduced in size and fail to acquire contractile phenotype due to dysregulated actin dynamics, leading to reduced blood pressure and impaired vascular remodeling after injury. Additionally, intestinal development is normal in these mice, yet epithelial regeneration after injury was defective due to dysfunction of smooth muscle and myofibroblasts. miR-143−/− mice have no obvious phenotype, while miR-145−/− mice phenocopy miR-143/145−/−, both exhibiting impaired injury- induced vascular remodeling.	Essential for injury response	42, 121–123
	miR-183/96/182	miR-183/96/182 mice are viable, but the postnatal functional differentiation and synaptic connectivity of photoreceptors are defective, leading to progressive retinal degeneration. miR-182−/− mice are viable without obvious phenotype.		124, 125
	miR-132/212	miR-132/212 mice are viable. While the overt neuronal morphology is normal in these mice, they exhibit defects in synaptic transmission and plasticity in hippocampus and neocortex.		126
	miR-144/451	miR-144/451 and miR-451 mice phenotypically resemble each other. Both are viable, yet exhibit erythroid hyperplasia, splenomegaly, and a mild anemia.		127
	R-296/298	miR-296/298−/− mice are viable.		21
	miR-497–195	miR-497–195−/− mice are viable.		21
	miR-654–376b	miR-654–376b−/− mice are viable.		21
monocistronic miRNAs	miR-205	miR-205−/− mice exhibit neonatal lethality with severe skin defects, due to impaired expansion of hair follical stem cells.	Essential for development	21, 128
	miR-126	miR-126 mice exhibit embryonic and perinatal lethality at a 40% penetrance, with leaky vessels and frequent hemorrhage due to the loss of vascular integrity and defects in endothelial cell proliferation, migration, and angiogenesis.	Essential for development	129, 130
	miR-214	miR-214 mice are viable, with normal cardiac structure and function at baseline. However, in response to ischemia/reperfusion injury, these mice exhibit loss of cardiac contractility, increased apoptosis, and excessive fibrosis.	Essential for Injury response	131
	miR-150	miR-150−/− mice are viable, yet exhibit B1 cell expansion and an enhanced humoral immune response.		132
	miR-155	miR-155−/− mice are viable, yet they exhibit defective adaptive immunity. These mice have impaired T cell–dependent antibody responses and increased Th2 polarization and amplified Th2 cytokine production in T cells. They also display defective TNF and LT-α		133, 134
	miR-21	miR-21 mice are viable and appear developmentally normal. These mice exhibit an improved survival rate in DSS-induced fatal colitis through protecting against inflammation and tissue injury.		135
	miR-223	miR-223 mice are viable, yet they exhibit neutrophil hyperactivation, causing spontaneous inflammatory lung pathology, and exaggerated tissue destruction after endotoxin challenge.		136
	miR-375	miR-375 mice are viable, but are hyperglycemic. They exhibit increased total pancreatic alpha-cell numbers, fasting and fed plasma glucagon levels, and increased gluconeogenesis and hepatic glucose output.		137
	miR-675	miR-675 resides in the exon1 of a non-coding RNA H19, a maternally imprinted gene. Mice deficient for H19 exon1 are viable, yet show defective muscle regeneration that can be rescued by exogenous miR-675 expression.		138
	miR-122	miR-122−/− mice are viable and developmentally normal. However, they develop steatohepatitis, liver fibrosis, and hepatocellular carcinoma when they are aged, due to impaired fat metabolism and cell proliferation in hepatocytes. In addition, miR-122 plays a non- canonical role in the life cycle of hepatitis C virus (HCV) by promoting the viral replication.	Essential for stress response	99, 101
	miR-140	miR-140 mice are viable, yet exhibit a mild growth retardation due to impaired skeletal development. In addition, these mice also exhibit Osteoarthritis-like changes upon aging, due to defective cartilage homeostasis.		139
	miR-33	miR-33−/− mice are viable, yet exhibit higher serum HDL cholesterol level, and enhanced cholesterol efflux in macrophages.		140
	miR-22	miR-22 mice are viable, yet they exhibit impaired cardiac intracellular calcium homeostasis and increased sensitivity to hemodynamic stress.		141, 142
	miR-210	miR-210−/− mice are viable.		21
	miR-688	miR-688−/− mice are viable.		21