Table 1. Abnormal phenotypes observed in mice after knocking out one or more members of a very broadly conserved miRNA family.
This table lists results for 20 of the 27 murine miRNA families conserved since the bilaterian ancestor (Table S1). With regard to the other seven families, for four (miR-183, miR-193, 216a, and miR-365) a member has been knocked out but only in the context of a deletion that also removes one or two miRNAs from other families (Table 3), which complicates attribution of the phenotypes, and for the remaining three a mouse knockout has yet to be reported. Some strains have more than one miRNA gene disrupted; multiple miRNAs from a disrupted polycistronic locus are linked with a tilde (~), whereas those from distant loci are separated with a comma.
| miRNA family (# of genes) | miRNA(s) removed | Phenotype |
|---|---|---|
| miR-1/206 (3) | miR-1-1, miR-1-2 | Postnatal lethality before weaning, complete penetrance, due to heart defects (Heidersbach et al., 2013; Wei et al., 2014) |
| miR-206 | Abnormal airway smooth muscle innervation (Radzikinas et al., 2011); reduced regeneration of muscle and neuromuscular junctions after injury; accelerated pathology in neuromuscular disease models (ALS, Duchenne muscular dystrophy) (Williams et al., 2009; Liu et al., 2012) | |
| miR-7 (3) | miR-7a-2 | Male and female infertility with hypogonadism due to pituitary defect (Ahmed et al., 2017); abnormal function of pancreatic beta cells (Latreille et al., 2014) |
| let-7/miR-98 (12) | let7c-2 ~ let7b | Modest intestinal hypertrophy, with increased crypt fission (Madison et al., 2013); increase in megakaryocyte–erythroid progenitors and decrease in granulocyte–monocyte progenitors (Rowe et al., 2016); faster liver regeneration after resection (Wu et al., 2015) |
| miR-9 (3) | miR-9-2, miR-9-3 | Postnatal lethality, complete penetrance; abnormal brain development (Shibata et al., 2011) |
| miR-9-3 | Male and female infertility (Shibata et al., 2011) | |
| miR-10 (2) | miR-10a | Increased intestinal adenomas in sensitized background (Apc) (Stadthagen et al., 2013) |
| miR-10b | Enlarged spleen with expansion of germinal centers; reduced tumorigenesis of breast cancer in sensitized background (MMTV-PyMT) (Kim et al., 2016b) | |
| miR-22 (1) | miR-22 | Reduced response of Th17 cells (Lu et al., 2015b); stress-induced cardiac dilation and contractile dysfunction (Gurha et al., 2012; Huang et al., 2013); reduced pathology in two disease models |
| miR-29 (4) | miR-29b-1 ~ 29a, | Embryonic lethality, partial penetrance, with death of survivors at ~4 weeks |
| miR-29b-2 ~ 29c | (Dooley et al., 2016; Sassi et al., 2017) | |
| miR-29b-1 ~ 29a | Reduced lifespan; decreased body weight; progressive locomotor impairment and ataxia with Purkinje cell defects; reduced numbers of hematopoietic stem and progenitor cells; premature thymic involution; perturbed development of Th1 cells and other lymphoid cells; reduced susceptibility to induced autoimmune disease (Papadopoulou et al., 2011; Smith et al., 2012; Hu et al., 2015; Papadopoulou et al., 2015); reduced pathology in models of obesity and arthritis (Dooley et al., 2016; van Nieuwenhuijze et al., 2017) | |
| miR-29b-2 ~ 29c | Reduced pathology in models of obesity, arthritis, and heart disease (Dooley et al., 2016; Sassi et al., 2017; van Nieuwenhuijze et al., 2017) | |
| miR-31 (1) | miR-31 | Perturbed T cell response and function; improved recovery from lymphocytic choriomeningitis virus infection; reduced pathology in model of autoimmune encephalomyelitis (Zhang et al., 2015; Moffett et al., 2017); increased tumorigenesis in model of colorectal cancer (Liu et al., 2017) |
| miR-33 (1) | miR-33 | Increased cholesterol efflux and serum HDL (Horie et al., 2010); increased ApoE lipidation and Aβ degradation in the brain (Kim et al., 2015); increased obesity and liver steatosis on high-fat diet (Horie et al., 2013); reduced fibrosis in model of heart disease (Nishiga et al., 2017) |
| miR-34/449 (6) | miR-34a, miR-34b ~ 34c, miR-449c ~ 449b ~ 449a | Postnatal lethality, incomplete penetrance; growth retardation; male and female infertility, and respiratory dysfunction due to defective motile cilia (Song et al., 2014) |
| miR-34b ~ 34c, miR-449c ~ 449b ~ 449a | Postnatal lethality, incomplete penetrance; growth retardation; abnormal brain development; male and female infertility and pulmonary pathology due to defective motile cilia (Wu et al., 2014); mitotic spindle orientation defects, neurogenesis defects with increased radial glial cells and decreased cortical neurons; thinner brain cortex (Fededa et al., 2016) | |
| miR-34a, miR-34b ~ 34c | Resilience to stress-induced anxiety (Andolina et al., 2016); increased tumorigenesis in several sensitized backgrounds | |
| miR-34a | Increased bone resorption (Krzeszinski et al., 2014); increased tumorigenesis in several sensitized backgrounds | |
| miR-25/32/92/ 363/367 (7) | miR-92a-1 | Embryonic lethality, partial penetrance; smaller size; minor skeletal defects (Penzkofer et al., 2014; Han et al., 2015); reduced pathology in model of kidney disease (Henique et al., 2017) |
| miR-96 (1) | miR-96 | Progressive hearing loss caused by sensory hair-cell degeneration due to arrested development of hair cells and auditory nerve connections (Lewis et al., 2009; Mencia et al., 2009; Kuhn et al., 2011) |
| miR-124 (3) | miR-124-1 | Postnatal lethality, incomplete penetrance; reduced brain size and abnormal brain development with increased neuronal apoptosis, aberrant axon sprouting in hippocampal dentate granule neurons, and reduced retinal cone photoreceptor cells (Sanuki et al., 2011) |
| miR-125 (3) | miR-125a | Defective differentiation of Treg cells; disrupted immune homeostasis with increased inflammation in immune disease models (Pan et al., 2015); perturbed development of kidneys and seminal vesicles; myeloproliferative disorder (Tatsumi et al., 2016) |
| miR-133 (3) | miR-133a-1, miR-133a-2 | Perinatal lethality, incomplete penetrance, due to heart defects; adult heart failure (Liu et al., 2008); defective skeletal muscle development and function (Liu et al., 2011); increased browning of white adipose tissue (Liu et al., 2013) |
| miR-184 (1) | miR-184 | Increased pancreatic beta cell proliferation and mass; decreased fasting blood glucose levels and increased fasting plasma insulin levels (Tattikota et al., 2014); thicker epidermis due to increased epidermal cell proliferation 29198823 |
| miR-200bc/429 (3) | miR-200b, miR-429 | Female infertility due to pituitary defect (Hasuwa et al., 2013) |
| miR-429 | Liver inflammation and dysfunction (Chen et al., 2018) | |
| miR-210 (1) | miR-210 | Increased spontaneous autoantibodies (Mok et al., 2013); increased differentiation of Th17 cells with increased pathology in immune disease model (colitis) (Wang et al., 2014); decreased pathology in pulmonary hypertension model (White et al., 2015) |
| miR-219 (2) | miR-219-1, miR-219-2 | Mostly penetrant neonatal lethality; knockout in oligodendrocytes causes myelination defects with tremors beginning at week 3, progressing to severe seizures, ataxia and death by ~4 months (Wang et al., 2017) |
| miR-219-2 | Tremors at adulthood (Wang et al., 2017) | |
| miR-375 (1) | miR-375 | Increased pancreatic alpha cells and decreased beta cells; hyperglycemia (Poy et al., 2009); altered membrane potential of beta cells (Salunkhe et al., 2015) |