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

A physiological examination of mice harboring a null allele at the aryl hyd rocarbon (Ah) locus revealed that the encoded aryl hydrocarbon receptor pla ys a role in the resolution of fetal vascular structures during development , Although the aryl hydrocarbon receptor is more commonly studied for its r ole in regulating xenobiotic metabolism and dioxin toxicity, a developmenta l role of this protein is supported by the observation that Ah null mice di splay smaller livers, reduced fecundity, and decreased body weights. Upon i nvestigating the liver phenotype, we found that the decrease in liver size is directly related to a reduction in hepatocyte size. We also found that s maller hepatocyte size is the result of massive portosystemic shunting in n ull animals. Colloidal carbon uptake and microsphere perfusion studies indi cated that 56% of portal blood flow bypasses the liver sinusoids. Latex cor rosion casts and angiography demonstrated that shunting is consistent with the existence of a patent ductus venosus in adult animals. Importantly, fet al vascular structures were also observed at other sites. Intravital micros copy demonstrated an immature sinusoidal architecture in the liver and pers istent hyaloid arteries in the eyes of adult Ah null mice, whereas corrosio n casting experiments described aberrations in kidney vascular patterns.