PATENT DUCTUS-ARTERIOSUS AND NEONATAL DEATH IN PROSTAGLANDIN RECEPTOREP4-DEFICIENT MICE

The physiological role of the prostaglandin E-2 receptor EP4 subtype w as investigated by generation of EP4-deficient mice by gene targeting. Loss of the EP4 receptor was not lethal in 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 partia lly closed in the survivors. In situ hybridization study showed that E P4 mRNA was strongly expressed in the ductus. These results suggest th at neonatal death is at least partly due to patent ductus arteriosus a nd that the EP4 receptor plays a role in regulation of the patency of this vessel. They also indicate that normal function of the EP4 recept or is essential in neonatal adaptation of the circulatory system. (C) 1998 Academic Press.