CoChat
Sign Up
Cited by 377Liver physiology and pathologyCardiovascular Conditions and TreatmentsToxic Organic Pollutants Impact

Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice

Open access
Lahvis, Garet P., Lindell, Susanne L., Thomas, Russell S., McCuskey, Robert S., Murphy, Christopher, Glover, Edward, Bentz, Michael, Southard, James +1 more·2000·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.190256997PMC PMC27043
Open this paper in CoChat — free account

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.190256997

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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., 2000

    The Results report that angiography and corrosion casts showed a shunt indicative of a patent ductus venosus in Ah-null mice. The casts showed the abnormal filling pattern in all Ah-null livers examined, but the paper does not establish 100% penetrance across Ah-null mice. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • 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., 2000

    The Results report a clearly visible shunt consistent with patent ductus venosus in male and female AHR-deficient mice, supporting its association with AHR deficiency. The paper does not establish that this phenotype is among the easiest to assess or provide a penetrance rate to support the comparative claim. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • 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., 2000

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

2 of the 53 references couldn’t be matched to a known paper.

Research works printed but not linked: 9

  1. [6]Eisen H J, Hannah R R, Legraverend C, Okey A B, Nebert D W. Biochem Actions Horm. 1983;10:227–257. [Google Scholar]
  2. [8]Pitot H C, Goldsworthy T, Campbell H A, Poland A. Cancer Res. 1980;40:3616–3620. [PubMed] [Google Scholar]
  3. [25]Agresti A. Stat Sci. 1992;7:131–135. [Google Scholar]
  4. [29]Francavilla A, Ove P, Polimeno L, Coetzee M, Makowka L, Barone M, Van Thiel D H, Starzl T E. Transplant Proc. 1988;20:494–497. [PMC free article] [PubMed] [Google Scholar]
  5. [33]Dubuisson L, Bioulac-Sage P, Bedin C, Balabaud C. J Submicrosc Cytol. 1984;16:283–287. [PubMed] [Google Scholar]
  6. [35]Healey J E. Ann NY Acad Sci. 1970;170:8–17. [Google Scholar]
  7. [36]Pons H A, Morgan J S, Hutchinson M, Rojkind M, Groszmann R J, Stadecker M J. Am J Trop Med Hyg. 1989;41:189–197. [PubMed] [Google Scholar]
  8. [37]McCuskey R S, Ekataksin W, LeBouton A V, Nishida J, Krasovich M A, McDonnell D, Williams C, Koldovsky O. In: Cells of the Hepatic Sinusoid VI. Wisse E, Knook D L, Balabaud C, editors. Leiden: Kupffer Cell Foundation; 1997. pp. 67–70. [Google Scholar]
  9. [50]Gu Y-Z, Hogenesch J, Bradfield C. Annu. Rev. Pharmacol. Toxicol. Academic Press; 2000. pp. 519–561. [DOI] [PubMed] [Google Scholar]

Cited by

Sorted by citations

Related

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.
ORCID
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
DOI
10.1073/pnas.190256997
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
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 › Radiology, Nuclear Medicine and Imaging › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review