Edn2, also known as endothelin-2, is a vasoactive peptide. It is involved in multiple physiological and pathological processes. In the ovary, it is a key regulator of follicle rupture, inducing follicular contraction immediately before ovulation [4]. In the retina, it has a role in protecting photoreceptors from injury [2,3]. Hypoxia-inducible factor 1A (HIF1A) and microRNA-210 (miR-210) are implicated in its regulation, with glycerol-3-phosphate dehydrogenase 1-like gene (GPD1L) being a miR-210 target that affects EDN2 levels [1].

In the context of gene knockout models, Edn2 knockout in mice carrying homozygous Pde6b(rd1) alleles or the Tg(RHO P347S) transgene led to increased photoreceptor survival, suggesting that increased Edn2 expression is protective to mutant photoreceptors [3]. In conditional Edn2 knockout (Edn2-iKO) mice, deletion of Edn2 suppressed acute lung inflammation by reducing neutrophil-mediated IFNγ/STAT1/IL-1β/NFĸB signaling cascade during acute lung injury [5].

In conclusion, Edn2 plays essential roles in ovarian follicle rupture, photoreceptor protection, and is involved in inflammatory regulation in the lung. Gene knockout models, such as the Edn2-iKO mouse model, have provided valuable insights into its functions in these biological processes and disease conditions like inherited photoreceptor degeneration and acute lung injury.