title: Patent ductus arteriosus and neonatal death in prostaglandin receptor EP4-deficient mice.
abstract: The physiological role of the prostaglandin E2 receptor EP4 subtype was 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 partially closed in the survivors. In situ hybridization 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.
authors.affiliation: Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Segi
authors.forename: Y
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: A
authors.initials: A
authors.lastname: Yamasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Aze
authors.forename: H
authors.initials: H
authors.lastname: Oida
authors.forename: T
authors.initials: T
authors.lastname: Nishimura
authors.forename: T
authors.initials: T
authors.lastname: Murata
authors.forename: T
authors.initials: T
authors.lastname: Matsuoka
authors.forename: F
authors.initials: F
authors.lastname: Ushikubi
authors.forename: M
authors.initials: M
authors.lastname: Hirose
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: N
authors.initials: N
authors.lastname: Yoshida
authors.forename: S
authors.initials: S
authors.lastname: Narumiya
authors.forename: A
authors.initials: A
authors.lastname: Ichikawa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015232:Dinoprostone / Q000502:physiology; D004373:Ductus Arteriosus / Q000473:pathology; D004374:Ductus Arteriosus, Patent / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D017403:In Situ Hybridization; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D058309:Receptors, Prostaglandin E, EP4 Subtype
chemical_list: D017931:DNA Primers; C545651:Ptger4 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015232:Dinoprostone