Patent ductus arteriosus and neonatal death in prostaglandin receptor EP4-deficient mice

E Segi, Y Sugimoto, A Yamasaki, Y Aze, H Oida… - Biochemical and …, 1998 - Elsevier
E Segi, Y Sugimoto, A Yamasaki, Y Aze, H Oida, T Nishimura, T Murata, T Matsuoka…
Biochemical and biophysical research communications, 1998Elsevier
The physiological role of the prostaglandin E2receptor EP4 subtype was investigated by
generation of EP4-deficient mice by gene targeting. Loss of the EP4 receptor was not
lethalin utero, but most EP4 (−/−) neonates became pale and lethargic approximately 24 h
after birth and died within 72 h. Less than 5% of the EP4 (−/−) mice survived and grew
normally more than a year. Histological examination revealed that the ductus arteriosus in
dead neonates remained open, while it was partially closed in the survivors. In …
The physiological role of the prostaglandin E2receptor EP4 subtype was investigated by generation of EP4-deficient mice by gene targeting. Loss of the EP4 receptor was not lethalin utero,but most EP4 (−/−) neonates became pale and lethargic approximately 24 h after birth and died within 72 h. Less than 5% of the EP4 (−/−) mice survived and grew normally more than a year. Histological examination revealed that the ductus arteriosus in dead neonates remained open, while it was partially closed in the survivors.In situhybridization study showed that EP4 mRNA was strongly expressed in the ductus. These results suggest that neonatal death is at least partly due to patent ductus arteriosus and that the EP4 receptor plays a role in regulation of the patency of this vessel. They also indicate that normal function of the EP4 receptor is essential in neonatal adaptation of the circulatory system.
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