Key result
Knockout of the GC-A receptor in mouse embryos led to hydrops fetalis in 33.3% of GC-A(-/-) embryos by embryonic day 17.5, all of which were dead, demonstrating its role in vascular development.
The endogenous ANP/BNP-GC-A system is essential for embryonic vascular development and organ morphogenesis, as its absence leads to hydrops fetalis and embryonic lethality in mice.
GC-A deletion causes embryonic lethality in mice; leaves open natriuretic peptide roles in human development.
Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) bind to the receptor guanylyl cyclase (GC)-A, leading to diuresis, natriuresis, and blood vessel dilation. In addition, ANP and BNP have various angiogenic properties in ischemic tissue. When breeding mice devoid of GC-A, we noted significant skewing of the Mendelian ratio in the offspring, suggesting embryonic lethality due to knockout of GC-A. Consequently, we here investigated the roles of endogenous ANP and BNP in embryonic neovascularization and organ morphogenesis. Embryos resulting from GC-A(-/-) × GC-A(+/-) crosses developed hydrops fetalis (HF) beginning at embryonic day (E)14.5. All embryos with HF had the genotype GC-A(-/-). At E17.5, 33.3% (12 of 36) of GC-A(-/-) embryos had HF, and all GC-A(-/-) embryos with HF were dead. Beginning at E16.0, HF-GC-A(-/-) embryos demonstrated poorly developed superficial vascular vessels and sc hemorrhage, the fetal side of the placenta appeared ischemic, and vitelline vessels on the yolk sac were poorly developed. Furthermore, HF-GC-A(-/-) embryos also showed abnormal constriction of umbilical cord vascular vessels, few cardiac trabeculae and a thin compact zone, hepatic hemorrhage, and poor bone development. Electron microscopy of E16.5 HF-GC-A(-/-) embryos revealed severe vacuolar degeneration in endothelial cells, and the expected 3-layer structure of the smooth muscle wall of the umbilical artery was indistinct. These data demonstrate the importance of the endogenous ANP/BNP-GC-A system not only in the neovascularization of ischemic tissues but also in embryonic vascular development and organ morphogenesis.
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Tokudome et al. (2015) studied Embryonic vascular and organ development (n=36). GC-A knockout was evaluated on Hydrops fetalis at embryonic day 17.5. Knockout of the GC-A receptor in mouse embryos led to hydrops fetalis in 33.3% of GC-A(-/-) embryos by embryonic day 17.5, all of which were dead, demonstrating its role in vascular development.
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