title: Loss of the major duodenal papilla results in brown pigment biliary stone formation in pdx1 null mice.
abstract: OBJECTIVE
  Pdx1 plays a pivotal role in pancreas organogenesis and specification of some types of cells in the duodenum and antral stomach. However, its expression is not restricted to pancreas, duodenum, and antral stomach but is also found in the common bile duct during embryogenesis. This study aimed to elucidate the role of Pdx1 in the development of the common bile duct, major duodenal papilla, and duodenum.
  
  
  METHODS
  Expression pattern of pdx1 during embryogenesis and the morphology of the common bile duct, major duodenal papilla, and duodenum in pdx1 null mice were analyzed.
  
  
  RESULTS
  The major duodenal papilla, peribiliary glands, and mucin-producing cells in the common bile duct were not formed in pdx1 null mice. Pdx1 null mice had shorter periampullary duodenal villi than wild-type mice at postnatal stages associated with reduced cell proliferation and increased apoptosis of the duodenal epithelial cells. Loss of the major duodenal papilla allowed duodeno-biliary reflux and bile infection, resulting in the formation of brown pigment biliary stones in pdx1 null mice, and antibiotics treatment significantly reduced the incidence of biliary stone formation.
  
  
  CONCLUSIONS
  Pdx1 is required for proper development of the major duodenal papilla, peribiliary glands, and mucin-producing cells in the common bile duct and for maintenance of the periampullary duodenal epithelial cells during perinatal period. Bile infection because of loss of the major duodenal papilla plays a significant role in the formation of brown pigment biliary stones in pdx1 null mice.
authors.affiliation: Department of Surgery and Surgical Basic Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Fukuda
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Furuyama
authors.forename: Sota
authors.initials: S
authors.lastname: Kodama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kuhara
authors.forename: Masashi
authors.initials: M
authors.lastname: Horiguchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Koizumi
authors.forename: Koji
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Doi
authors.forename: Christopher V E
authors.initials: CV
authors.lastname: Wright
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
mesh_terms: D014670:Ampulla of Vater / Q000196:embryology* / Q000382:microbiology / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D018988:Bacterial Translocation; D049109:Cell Proliferation; D002769:Cholelithiasis / Q000209:etiology*; D003135:Common Bile Duct / Q000196:embryology* / Q000382:microbiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
chemical_list: D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein