Sox17 haploinsufficiency results in perinatal biliary atresia and hepatitis in C57BL/6 background mice

Mami Uemura, Aisa Ozawa, Takumi Nagata, Kaoruko Kurasawa, Naoki Tsunekawa, Ikuo Nobuhisa, Tetsuya Taga, Kenshiro Hara, Akihiko Kudo, Hayato Kawakami, Yukio Saijoh, Masamichi Kurohmaru, Masami Kanai-Azuma, Yoshiakira Kanai

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


Congenital biliary atresia is an incurable disease of newborn infants, of unknown genetic causes, that results in congenital deformation of the gallbladder and biliary duct system. Here, we show that during mouse organogenesis, insufficient SOX17 expression in the gallbladder and bile duct epithelia results in congenital biliary atresia and subsequent acute 'embryonic hepatitis', leading to perinatal death in ~95% of the Sox17 heterozygote neonates in C57BL/6 (B6) background mice. During gallbladder and bile duct development, Sox17 was expressed at the distal edge of the gallbladder primordium. In the Sox17+/- B6 embryos, gallbladder epithelia were hypoplastic, and some were detached from the luminal wall, leading to bile duct stenosis or atresia. The shredding of the gallbladder epithelia is probably caused by cell-autonomous defects in proliferation and maintenance of the Sox17+/- gallbladder/bile duct epithelia. Our results suggest that Sox17 plays a dosage-dependent function in the morphogenesis and maturation of gallbladder and bile duct epithelia during the late-organogenic stages, highlighting a novel entry point to the understanding of the etiology and pathogenesis of human congenital biliary atresia.

Original languageEnglish
Pages (from-to)639-648
Number of pages10
JournalDevelopment (Cambridge)
Issue number3
Publication statusPublished - 2013 Feb 1
Externally publishedYes


  • Bile duct
  • Biliary atresia
  • Gallbladder
  • Haploinsufficiency
  • Hepatitis
  • Mouse
  • Sox17

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology


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