Table 1.
Mouse phenotypes
| Disrupted gene | Phenotype | References | |
|---|---|---|---|
| Mef2 transcription factors | |||
| Mef2a | Perinatal death (cardiac sudden death), mitochondrial defects | [30] | |
| Mef2b | Normal cardiac development | [32] | |
| Mef2c | Embryonic death by day 9.5, cardiovascular defects, defects of smooth muscle cell differentiation | [28] | |
| Mef2c (endothelial-specific deletion) | Promotion of vascular growth in oxygen-induced retinopathy | [31] | |
| Mef2d | Resistance to cardiac hypertrophy induced by pressure overload | [33] | |
| Ets and Foxc transcription factors | |||
| Etv2 | Embryonic death by day 10.5, defects of blood and vessel development | [2, 37] | |
| Etv2 (endothelial-specific deletion) | No obvious phenotype in steady state condition | [131] | |
| Foxc1 | Prenatal and perinatal death, cardiovascular abnormalities, skeletal defects | [40–42] | |
| Foxc2 | Prenatal and perinatal death, cardiovascular and lymphatic abnormalities, skeletal defects | [38, 39] | |
| Foxc1 and Foxc2 | Embryonic death by day 9.5, more severe defects of cardiovascular and lymphatic development than Foxc1 or Foxc2-null mice | [41, 43, 44] | |
| Foxo transcription factors | |||
| Foxo1 | Embryonic death by day 10.5–11, vasculature defects | [50, 51] | |
| Foxo1 (endothelial-specific deletion) | Embryonic death by day 11, vasculature defects | [52] | |
| Foxo3 | Age-dependent infertility, abnormality of ovarian follicular development | [50, 51] | |
| Foxo4 | Normal | [50, 51] | |
| Foxo6 | Defects of memory consolidation | [58] | |
| VEGF signaling | |||
| VEGF (heterozygous deletion) | Embryonic death by day 12, abnormality of vascular development | [65, 66] | |
| VEGFR2 | VEGF receptor | Embryonic death by day 9.5, defects of hematopoietic and endothelial cell development | [67] |
| PI3K-Akt signaling | |||
| p110α (general or endothelial-specific inactivation) | Class IA PI3K subunit | Embryonic death by day 12.5, vascular defects | [85] |
| p85α and p85β | Class IA PI3K subunit | Embryonic death by day 11.5, vascular defects, hemorrhage | [86] |
| PI3K-C2α (general or endothelial-specific deletion) | Class II PI3K subunit | Embryonic death by days 11.5–12.5, vascular defects, hemorrhage | [87] |
| Akt1 | Growth retardation, reduction of vascularization in placenta | [88, 89] | |
| Akt1 (endothelial-specific postnatal deletion) | Reduction of vascular development in retina | [90] | |
| mTOR signaling | |||
| Raptor | mTORC1 subunit | Embryonic death at early stages of development | [97] |
| Raptor (endothelial cell-specific deletion) | Embryonic death | [98] | |
| Rictor | mTORC2 subunit | Embryonic death by day 11.5, growth arrest, placental abnormalities | [97, 99] |
| Rictor (endothelial cell-specific deletion) | Embryonic death by days 11.5–12.5, growth retardation, reduction of peripheral vascularization | [98, 100] | |
| Notch signaling | |||
| Notch1 | Notch receptor | Embryonic death by day 11.5, delayed and disorganized somitogenesis | [120, 121] |
| Notch4 | Notch receptor | Normal | [122] |
| Notch1 and Notch4 | More severe phenotype than Notch1-null mice, defects of vascular remodeling | [122] | |
| Dll4 (heterozygous deletion) | Notch ligand | Similar to phenotype of Notch1 and Notch4-null mice, defects of vascular remodeling | [123] |
| RBP-j | Notch transcriptional effector | Defects of vascular remodeling and somite formation | [123] |
| Hey1 | Notch target gene | Normal | [124] |
| Hey2 | Notch target gene | Cardiac hypertrophy after birth | [125] |
| Hey1 and Hey2 | Embryonic death by days 9.5–11.5, defects of vascular remodeling, hemorrhage | [124, 126] | |
| Hes1 | Notch target gene | No obvious phenotype in vascular development | [127] |
| Hes5 | Notch target gene | Normal | [127] |
| Hes1 and Hes5 (general or endothelial-specific deletion of Hes1 on Hes5-null background) | Defects of vascular remodeling in the brain | [127] | |