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

Garet P. Lahvis, Susanne L. Lindell, Russell S. Thomas, Robert S. McCuskey, Christopher J Murphy, Edward Glover, Michael Bentz, James Southard, Christopher A. Bradfield

Research output: Contribution to journalArticle

284 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)10442-10447
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number19
StatePublished - Sep 12 2000
Externally publishedYes

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Blood Vessels
Fetus
Hydrocarbons
Liver
Aryl Hydrocarbon Receptors
Hepatocytes
Corrosion Casting
Persistent Hyperplastic Primary Vitreous
Dioxins
Corrosion
Latex
Xenobiotics
Microspheres
Fertility
Angiography
Carbon
Perfusion
Alleles
Body Weight
Mouse Ahr protein

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice. / Lahvis, Garet P.; Lindell, Susanne L.; Thomas, Russell S.; McCuskey, Robert S.; Murphy, Christopher J; Glover, Edward; Bentz, Michael; Southard, James; Bradfield, Christopher A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 19, 12.09.2000, p. 10442-10447.

Research output: Contribution to journalArticle

Lahvis, GP, Lindell, SL, Thomas, RS, McCuskey, RS, Murphy, CJ, Glover, E, Bentz, M, Southard, J & Bradfield, CA 2000, 'Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice', Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 19, pp. 10442-10447.
Lahvis, Garet P. ; Lindell, Susanne L. ; Thomas, Russell S. ; McCuskey, Robert S. ; Murphy, Christopher J ; Glover, Edward ; Bentz, Michael ; Southard, James ; Bradfield, Christopher A. / Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 19. pp. 10442-10447.
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