RT Journal Article SR Electronic T1 The Aryl Hydrocarbon Receptor Is Required for Developmental Closure of the Ductus Venosus in the Neonatal Mouse JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 714 OP 720 DO 10.1124/mol.104.008888 VO 67 IS 3 A1 Garet P. Lahvis A1 Robert W. Pyzalski A1 Edward Glover A1 Henry C. Pitot A1 Matthew K. McElwee A1 Christopher A. Bradfield YR 2005 UL http://molpharm.aspetjournals.org/content/67/3/714.abstract AB A developmental role for the Ahr locus has been indicated by the observation that mice harboring a null allele display a portocaval vascular shunt throughout life. To define the ontogeny and determine the identity of this shunt, we developed a visualization approach in which three-dimensional (3D) images of the developing liver vasculature are generated from serial sections. Applying this 3D visualization approach at multiple developmental times allowed us to demonstrate that the portocaval shunt observed in Ahr-null mice is the remnant of an embryonic structure and is not acquired after birth. We observed that the shunt is found in late-stage wild-type embryos but closes during the first 48 h of postnatal life. In contrast, the same structure fails to close in Ahr-null mice and remains open throughout adulthood. The ontogeny of this shunt, along with its 3D position, allowed us to conclude that this shunt is a patent developmental structure known as the ductus venosus (DV). Upon searching for a physiological cause of the patent DV, we observed that during the first 48 h, most major hepatic veins, such as the portal and umbilical veins, normally decrease in diameter but do not change in Ahr-null mice. This observation suggests that failure of the DV to close may be the consequence of increased blood pressure or a failure in vasoconstriction in the developing liver.