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Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice
Open accessAbstract
A physiological examination of mice harboring a null allele at the aryl hydrocarbon ( Ah ) locus revealed that the encoded aryl hydrocarbon receptor plays a role in the resolution of fetal vascular structures during development. Although the aryl hydrocarbon receptor is more commonly studied for its role in regulating xenobiotic metabolism and dioxin toxicity, a developmental role of this protein is supported by the observation that Ah null mice display smaller livers, reduced fecundity, and decreased body weights. Upon investigating the liver phenotype, we found that the decrease in liver size is directly related to a reduction in hepatocyte size. We also found that smaller hepatocyte size is the result of massive portosystemic shunting in null animals. Colloidal carbon uptake and microsphere perfusion studies indicated that 56% of portal blood flow bypasses the liver sinusoids. Latex corrosion casts and angiography demonstrated that shunting is consistent with the existence of a patent ductus venosus in adult animals. Importantly, fetal vascular structures were also observed at other sites. Intravital microscopy demonstrated an immature sinusoidal architecture in the liver and persistent hyaloid arteries in the eyes of adult Ah null mice, whereas corrosion casting experiments described aberrations in kidney vascular patterns.
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“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., 2000
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“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., 2000
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“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., 2000
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Metadata
- Authors
- Lahvis, G. P., Lindell, S. L., Thomas, R. S., McCuskey, R. S., Murphy, C., Glover, E., Bentz, M., Southard, J., & Bradfield, C. A.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Bradfield, Christopher A.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-09-05
- Volume
- 97
- Issue
- 19
- Pages
- 10442-10447
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC27043
- OpenAlex
- W2163212976
- Cited by
- 377
- References
- 53
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 12 · 2021: 13 · 2020: 7 · 2019: 8 · 2018: 14 · 2017: 10 · 2016: 14 · 2015: 8 · 2014: 11 · 2013: 13 · 2012: 19
- FWCI
- 12.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Burroughs Wellcome Fund
- Colgate-Palmolive Company
- National Institutes of Health (5p30ca007175-36, CA22484)
- National Cancer Institute (CA-07175, T32CA009681, CA 22484, P01CA022484)
- National Institute of Environmental Health Sciences (ES06883, F32ES005877, R01ES006883)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Cardiovascular Conditions and Treatments
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Keywords
- aryl hydrocarbon receptor, portosystemic shunt, patent ductus venosus, hyaloid artery, liver development, hepatocyte size, dioxin toxicity
- MeSH terms
- Animals, Arteries, Eye, Female, Kidney, Liver, Male, Mice, Inbred C57BL, Organ Size, Receptors, Aryl Hydrocarbon, Mice
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