Document Detail


Sox17 haploinsufficiency results in perinatal biliary atresia and hepatitis in C57BL/6 background mice.
MedLine Citation:
PMID:  23293295     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  140     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-07     Completed Date:  2013-03-07     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  639-48     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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
Grant Support
ID/Acronym/Agency:
R01 HD066121/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/HMGB Proteins; 0/SOXF Transcription Factors; 0/Sox17 protein, mouse
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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