Hepatic artery malformations associated with a primary defect in intrahepatic bile duct development.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Clotman
Frédéric
F
Hormone and Metabolic Research Unit, Université catholique de Louvain and Institute of Cellular Pathology, Avenue Hippocrate 75, box 7529, B-1200 Brussels, Belgium. frederic.clotman@horm.ucl.ac.be
Libbrecht
Louis
L
Gresh
Lionel
L
Yaniv
Moshe
M
Roskams
Tania
T
Rousseau
Guy G
GG
Lemaigre
Frédéric P
FP
D000015:Abnormalities, Multiple / Q000196:embryology; D000818:Animals; D001237:Asphyxia / Q000209:etiology; D001653:Bile Ducts, Intrahepatic / Q000002:abnormalities* / Q000196:embryology*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D005314:Embryonic and Fetal Development; D006499:Hepatic Artery / Q000002:abnormalities* / Q000196:embryology*; D051539:Hepatocyte Nuclear Factor 1-beta; D051559:Hepatocyte Nuclear Factor 6; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D013577:Syndrome; D035441:Thoracic Wall / Q000002:abnormalities / Q000196:embryology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics
D004268:DNA-Binding Proteins; C496495:HNF1B protein, human; D051559:Hepatocyte Nuclear Factor 6; C496496:Hnf1b protein, mouse; D018398:Homeodomain Proteins; C496605:ONECUT1 protein, human; C496606:Onecut1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D051539:Hepatocyte Nuclear Factor 1-beta