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 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.
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Ahr null mice show a patent ductus venosus with complete penetrance.
“Mice null for Ahr exhibit a patent DV with 100% penetrance, though the AHR-driven genes responsible for shunt closer remain unknown.”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Lahvis et al., 2005
Early characterization of Ahr null mice from our own laboratory uncovered significant vascular phenotypes, including the patent ductus venosus in the liver and a hyaloid artery in the eye, both of which are normal fetal structures that typically resolve shortly after birth.
“Early characterization of these null mice from our own laboratory uncovered significant vascular phenotypes, including the patent ductus venosus (DV) in the liver and a hyaloid artery in the eye, both of which are normal fetal structures that typically resolve shortly after birth (Lahvis et al., 2000; Lahvis et al., 2005; J. V. Schmidt et al., 1996).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Lahvis et al., 2005
Ahrnls mice are resistant to TCDD-induced toxicity and exhibit a patent ductus venosus through adulthood.
“In early experiments employing this model, the Ahrnls mice were found to be resistant to TCDD-induced toxicity and exhibit a patent DV through adulthood.”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Lahvis et al., 2005
The Ahrnls model is a phenocopy of the Ahr null mouse.
“These observations suggest the Ahrnls model is a phenocopy of the Ahr null mouse (Bunger et al., 2003; Lahvis et al., 2005).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Lahvis et al., 2005
Patent ductus venosus is among the most easily assessed and penetrant AHR-mediated phenotypes.
“The patent DV is one of the most easily assessed and penetrant AHR-mediated phenotypes (Harstad et al., 2006; Lahvis et al., 2000; Lahvis et al., 2005).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Lahvis et al., 2005
The Arnt hypomorph exhibits patent DV with penetrance approaching that of the AhrΔ2 null mouse.
“The ARNT hypomorph mouse exhibits a patent DV with a penetrance approaching that of the AhrΔ2 null mouse (Lahvis et al., 2005; Walisser, Bunger, Glover, & Bradfield, 2004; Walisser, Bunger, Glover, Harstad, et al., 2004).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Lahvis et al., 2005
Cites
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Regulation of the immune response by the aryl hydrocarbon receptor
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Self-citation
- Authors
- Lahvis, G. P., Pyzalski, R. W., Glover, E., Pitot, H. C., McElwee, M. K., & Bradfield, C. A.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- Molecular Pharmacology
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 67
- Issue
- 3
- Pages
- 714-720
- ISSN
- 0026-895X (ISSN-L)
- OpenAlex
- W2154532970
- Cited by
- 168
- References
- 1
- Citations by year
- 2026: 4 · 2024: 2 · 2023: 6 · 2022: 5 · 2021: 9 · 2020: 8 · 2019: 2 · 2018: 7 · 2017: 10 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 12 · 2012: 6
- FWCI
- 6.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1f32es005887-01)
- National Cancer Institute (P01CA022484, P30CA014520)
- National Institute of Environmental Health Sciences (F32-ES05887, R01ES013566, F32ES005877)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiovascular Conditions and Treatments
- Health Sciences › Medicine › Surgery › Vascular anomalies and interventions
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- aryl hydrocarbon receptor, ductus venosus, portacaval shunt, hepatic vein, vasoconstriction, postnatal development
- MeSH terms
- Animals, Animals, Newborn, Capillaries, Cerebrovascular Circulation, Hepatic Veins, Image Processing, Computer-Assisted, Portal Vein, Vena Cava, Inferior, Receptors, Aryl Hydrocarbon, Mice, Knockout, Mice
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