TABLE 7.

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)	?