Received for publication November 3, 2004.
Revised December 7, 2004.
Accepted for publication December 7, 2004.

The aryl hydrocarbon receptor is required for developmental closure of the ductus venosus in the neonatal mouse

Abstract

A developmental role for the Ahr locus has been indicated by the observation that mice harboring a null allele display a porto-caval vascular shunt throughout life. To define the ontogeny and determine the identity of this shunt, we developed a visualization approach where 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 porto-caval 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 hours 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 hours, 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 pressure or a failure in vasoconstriction in the developing liver.

Key words: Ah receptor, Genetics, Knockout