title: Generation of a conditional allele of the mouse prostaglandin EP4 receptor.
abstract: Genetic disruption of the mouse EP4 receptor results in perinatal lethality associated with persistent patent ductus areteriosus (PDA). To circumvent this, an EP4 allele amenable to conditional deletion using the Cre/loxP system was generated. The targeting construct was comprised of a floxed exon2 in tandem with the neomycin-resistance gene in intron 2, flanked by third 3' LoxP site. Mice homozygous for the targeted allele (EP4(lox+neo/lox+neo)), or following its Cre-mediated deletion (EP4(del/del)), also die within hours of birth with PDA. In contrast, mice homozygous for a partially recombined allele, retaining exon2 but lacking neo (EP4(flox/flox)), are viable and show no overt phenotype. Postnatal deletion of the floxed EP4 gene is efficiently achieved in the liver and kidney in a transgenic mouse expressing the inducible Mx1Cre recombinase. The EP4(flox) mouse should provide a useful reagent with which to examine the physiologic roles of the EP4 receptor.
authors.affiliation: Division of Nephrology and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-2372, USA.
authors.forename: André
authors.initials: A
authors.lastname: Schneider
authors.forename: YouFei
authors.initials: Y
authors.lastname: Guan
authors.forename: Yahua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mark A
authors.initials: MA
authors.lastname: Magnuson
authors.forename: Cathy
authors.initials: C
authors.lastname: Pettepher
authors.forename: Charles D
authors.initials: CD
authors.lastname: Loftin
authors.forename: Robert
authors.initials: R
authors.lastname: Langenbach
authors.forename: Richard M
authors.initials: RM
authors.lastname: Breyer
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Breyer
mesh_terms: D000818:Animals; D001483:Base Sequence; D002678:Chimera; D003001:Cloning, Molecular; D017931:DNA Primers; D004374:Ductus Arteriosus, Patent / Q000235:genetics*; D017353:Gene Deletion; D006720:Homozygote; D019426:Integrases / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018078:Receptors, Prostaglandin E / Q000235:genetics*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; C045073:Cre recombinase; D019426:Integrases