Table 1.
Defects in mouse embryos lacking HIF transcription factors.
| KO mouse model/gene | Lethal by | Phenotypes
|
Reference | |
|---|---|---|---|---|
| In vitro hypoxic cultures | In vivo | |||
| Germline/HIFβ−/− | E10.5 | – No up-regulation of glycolytic enzyme genes in ES cells | – Developmental delay | Maltepe et al., 1997 |
| – No up-regulation of hypoglycemia genes in ES cells | – Defect in YS angiogenesis | |||
| – Lower VEGF level in YS and embryo proper | ||||
| Germline/HIFβ−/− | E9.5–10.5 | – Impaired neural development | [78] | |
| – Small fetal placenta and chorioallantoic plate | ||||
| – Defect in PL vascularization | ||||
| – Fetal placenta labyrinth cavities | ||||
| Germline/HIFβ−/− | Not mentioned | – Abnormal vessel organization | [64] | |
| – Less CD31+ cells throughout the embryo | ||||
| – Defect in chorio–allantoic fusion | ||||
| – Less VEGF expression in embryo | ||||
| – Failure of neural tube closure | ||||
| – Increased number of apoptotic cells in embryo | ||||
| Germline/HIF1α−/− | E11 | – Down-regulation of glycolytic enzyme genes in ES cells | – Developmental delay | [62] |
| – No up-regulation of Vegf | – Pericardial effusion | |||
| – Impaired ES cell proliferation | – Failure of neural tube closure | |||
| – Extensive mesenchymal cell death | ||||
| – Abnormal vascular structure in cephalic region | ||||
| Germline/HIF1α−/− | Not mentioned | – No up-regulation of glycolytic genes and Vegf in ES cells | – Increased level of hypoxia in embryo | Ryan et al., 1998 |
| – Increased number of apoptotic cells in embryo | ||||
| – Defective YS vascularization | ||||
| – Defective cephalic vascularization | ||||
| Conditional/HIF1αfl: Tie2Cre | Not lethal | – Less proliferation of endothelial cells | – Reduction in vessel density | Tang et al., 2004 |
| – Defect in elongation of endothelial cells | – Delayed wound healing | |||
| – Less VEGF level in culture medium | – Smaller, less necrotic, less vascularized tumor | |||
| – No induction of VEGF receptors | ||||
| Germline/HIF2α−/− | E9.5–E12.5 | – Vascular defect in YS and embryo proper | Feng et al., 2011 | |
| Germline/HIF2α−/− | E12.5–E16.5 | – Bradycardia | Tian et al., 1998 | |
| – Reduced level of catecholamine | ||||
| Germline/HIF2α−/− | E13.5 | – Cardiac failure | Compernolle et al., 2002 | |
| Neonatal stage | – Impaired lung maturation | |||