Clotman Frédéric, Libbrecht Louis, Gresh Lionel, Yaniv Moshe, Roskams Tania, Rousseau Guy G, Lemaigre Frédéric P
Hormone and Metabolic Research Unit, Université catholique de Louvain and Institute of Cellular Pathology, Avenue Hippocrate 75, box 7529, B-1200 Brussels, Belgium.
J Hepatol. 2003 Nov;39(5):686-92. doi: 10.1016/s0168-8278(03)00409-4.
BACKGROUND/AIMS: The portal tracts contain bile ducts associated with branches of the portal vein and of the hepatic artery. Hepatic artery malformations are found in diseases in which fetal biliary structures persist after birth (ductal plate malformations). Here we investigated how hepatic artery malformations relate to abnormal bile duct development.
Hepatic artery and biliary development was analyzed in fetuses with Jeune syndrome or Meckel syndrome, which show ductal plate malformations. We also analyzed hepatic artery development in transgenic mice which exhibit biliary anomalies following inactivation of the genes for hepatocyte nuclear factor (HNF)-6 or HNF-1beta, two transcription factors expressed in biliary cells, but not in arteries.
We show that arterial anomalies occurred in fetuses with Jeune syndrome or Meckel syndrome. We provide the first description of hepatic artery branch development in the mouse and show that inactivation of the Hnf6 or Hnf1beta gene results in anomalies of the hepatic artery branches. In the transgenic mice and in the human syndromes, the biliary anomalies preceded the arterial anomalies.
A primary defect in biliary epithelial cells is associated with hepatic artery malformations in mice. Our data provide a model to interpret and study hepatic artery anomalies in humans.
背景/目的：门管区包含与门静脉分支和肝动脉分支相关的胆管。肝动脉畸形见于出生后胎儿胆管结构持续存在的疾病（导管板畸形）。在此，我们研究了肝动脉畸形与胆管异常发育之间的关系。
对患有儒内综合征或梅克尔综合征的胎儿进行肝动脉和胆管发育分析，这些胎儿表现出导管板畸形。我们还分析了在肝细胞核因子（HNF）-6或HNF-1β基因失活后出现胆管异常的转基因小鼠的肝动脉发育情况，这两种转录因子在胆管细胞中表达，但不在动脉中表达。
我们发现儒内综合征或梅克尔综合征胎儿出现动脉异常。我们首次描述了小鼠肝动脉分支的发育情况，并表明Hnf6或Hnf1beta基因失活会导致肝动脉分支异常。在转基因小鼠和人类综合征中，胆管异常先于动脉异常出现。
胆管上皮细胞的原发性缺陷与小鼠肝动脉畸形有关。我们的数据提供了一个解释和研究人类肝动脉异常的模型。
