Phenotypes observed in apelin, apelin receptor, and apela knockout mouse models
The lack of similarity between apelin and apelin receptor knock-out mice prompted the suggestion that there might be another ligand at the receptor. Apela knock-outs largely phenocopy the receptor knock-outs, supporting the idea that ELA is the missing endogenous ligand.
| Apelin Knockout Mice | Apelin Receptor Knockout Mice | Apela Mutant Mice |
|---|---|---|
| Mendelian birth ratio (Kidoya et al., 2008; Charo et al., 2009) | Loss of homozygous mice (Ishida et al., 2004; Charo et al., 2009; Roberts et al., 2009; Scimia et al., 2012; Kang et al., 2013) | Loss of homozygous mice (Freyer et al., 2017; Ho et al., 2017) |
| Normal heart morphology (Kuba et al., 2007; Kidoya et al., 2008; Charo et al., 2009) | Severe cardiac and vascular developmental defects (Kang et al., 2013) | Severe cardiac and vascular developmental defects (Freyer et al., 2017; Ho et al., 2017) |
| Normal blood pressure (Charo et al., 2009) | Normal blood pressure (Ishida et al., 2004; Charo et al., 2009) | Pre-eclampsia (Ho et al., 2017) |
| Modest decrease in basal cardiac contractility (Charo et al., 2009) | Modest decrease in basal cardiac contractility (Charo et al., 2009) | ? |
| Marked decrease in exercise capacity (Charo et al., 2009) | Marked decrease in exercise capacity (Charo et al., 2009) | ? |
| Severe heart failure in response to pressure overload (Kuba et al., 2007) | Markedly reduced heart failure in response to pressure overload (Scimia et al., 2012) | ? |