Morphogenesis, regeneration and congenital disease in gallbladder and bile duct system in mammals

2017 Fiscal Year Final Research Report

• Project/Area Number: 24228005
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Basic veterinary science/Basic zootechnical science
• Research Institution: The University of Tokyo
• Principal Investigator: Yoshiakira Kanai 東京大学, 大学院農学生命科学研究科(農学部), 准教授 (30260326)
• Co-Investigator(Kenkyū-buntansha): 九郎丸 正道 東京大学, 大学院農学生命科学研究科(農学部), 教授 (00148636) ; 恒川 直樹 日本大学, 生物資源科学部, 教授 (50431838) ; 多屋 長治 公益財団法人東京都医学総合研究所, 基盤技術研究センター, 室長 (90175456)
• Project Period (FY): 2012-05-31 – 2017-03-31
• Keywords: 応用動物学 / 獣医学 / 疾患モデル / 胆道 / 胆嚢 / 肝外胆管 / 胆道閉鎖症 / マウス

Outline of Final Research Achievements

The gallbladder excretes cytotoxic bile acids to the duodenum through the cystic duct and common bile duct system. In this study, Sox17 haploinsufficiency causes the biliary atresia-like phenotypes and hepatitis in late organogenesis mouse embryos. Transcriptomic analyses revealed the early onset of cholecystitis in the Sox17+/- embryos, together with the appearance of ectopic cystic duct-like epithelia in their gallbladders. The Sox17+/- gallbladder also showed the drastic reduction in Sonic hedgehog expression, leading to aberrant smooth muscle formation and defective contraction of the fetal gallbladder. The defective gallbladder contraction positively correlated with the severity of embryonic hepatitis in Sox17+/- embryos, suggesting the contribution of embryonic cholecystitis and fetal gallbladder contraction in the early pathogenesis of mammalian biliary atresia.

Free Research Field

獣医学、発生生物学