| Sox17 haploinsufficiency results in perinatal biliary atresia and hepatitis in C57BL/6 background mice. | |
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MedLine Citation:
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PMID: 23293295 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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 |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Development (Cambridge, England) Volume: 140 ISSN: 1477-9129 ISO Abbreviation: Development Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-01-07 Completed Date: 2013-03-07 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 8701744 Medline TA: Development Country: England |
Other Details:
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Languages: eng Pagination: 639-48 Citation Subset: IM |
Affiliation:
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Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Bile Ducts / metabolism, pathology Biliary Atresia / genetics*, pathology Cell Proliferation Cholestasis / genetics, pathology Embryo, Mammalian / metabolism, pathology Endoplasmic Reticulum Stress Epithelium / metabolism, pathology Female Gallbladder / metabolism, ultrastructure Gene Expression Regulation, Developmental* HMGB Proteins / genetics, metabolism* Haploinsufficiency* Hepatitis, Animal / genetics, metabolism, pathology Hepatocytes / metabolism Heterozygote Immunohistochemistry Liver / metabolism, ultrastructure Male Mice Mice, Inbred C57BL Mice, Inbred ICR Pregnancy SOXF Transcription Factors / genetics, metabolism* Time Factors |
| Chemical | |
Reg. No./Substance:
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0/HMGB Proteins; 0/SOXF Transcription Factors; 0/Sox17 protein, mouse |
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