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

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  • Mami Uemura
    Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan
  • Aisa Ozawa
    Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan
  • Takumi Nagata
    Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan
  • Kaoruko Kurasawa
    Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan
  • Naoki Tsunekawa
    Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan
  • Ikuo Nobuhisa
    Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8510, Japan
  • Tetsuya Taga
    Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8510, Japan
  • Kenshiro Hara
    Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan
  • Akihiko Kudo
    Department of Anatomy, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan
  • Hayato Kawakami
    Department of Anatomy, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan
  • Yukio Saijoh
    Department of Neurobiology and Anatomy, The University of Utah, Salt Lake City, UT 84132-3401, USA
  • Masamichi Kurohmaru
    Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan
  • Masami Kanai-Azuma
    Center for Experimental Animal, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8510, Japan
  • Yoshiakira Kanai
    Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan

Bibliographic Information

Published
2013-02-01
Resource Type
journal article
DOI
  • 10.1242/dev.086702
Publisher
The Company of Biologists

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Description

<jats:p>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.</jats:p>

Journal

  • Development

    Development 140 (3), 639-648, 2013-02-01

    The Company of Biologists

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