Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice
Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice
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DOI：
10.1073/pnas.190256997
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发表时间：
2000-09-12
影响因子：
11.1
通讯作者：
Bradfield, CA
中科院分区：
文献类型：
--
作者：
Lahvis, GP;Lindell, SL;Bradfield, CA
对在芳烃（Ah）基因座处携带无效等位基因的小鼠的生理检查显示，编码的芳烃受体在发育期间胎儿血管结构的解析中起作用。尽管芳烃受体更常被研究其在调节异生物质代谢和二恶英毒性中的作用，这种蛋白质的发育作用得到了Ah缺失小鼠显示出较小的肝脏、降低的生殖力和降低的体重的观察结果的支持。在研究肝脏表型时，我们发现肝脏大小的减少与肝细胞大小的减少直接相关。我们还发现，较小的肝细胞大小是无效动物大量门体分流的结果。胶体碳摄取和微球灌注研究表明，56%的门静脉血流绕过肝窦。乳胶腐蚀模型和血管造影术表明，分流与成年动物存在未闭静脉导管一致。重要的是，在其他部位也观察到了胎儿血管结构。活体显微镜检查表明，在肝脏和持久的玻璃体动脉在成年阿空小鼠的眼睛中的一个不成熟的窦状结构，而腐蚀铸造实验描述的畸变肾血管图案。
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.