Generation of a conditional allele of the mouse prostaglandin EP ₄ receptor

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.