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

研究成果: Article査読

32 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)639-648
ページ数10
ジャーナルDevelopment (Cambridge)
140
3
DOI
出版ステータスPublished - 2013 2 1

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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