Document Detail


Mutation of zebrafish Snapc4 is associated with loss of the intrahepatic biliary network.
MedLine Citation:
PMID:  22222761     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Biliary epithelial cells line the intrahepatic biliary network, a complex three-dimensional network of conduits. The loss of differentiated biliary epithelial cells is the primary cause of many congenital liver diseases. We identified a zebrafish snapc4 (small nuclear RNA-activating complex polypeptide 4) mutant in which biliary epithelial cells initially differentiate but subsequently disappear. In these snapc4 mutant larvae, biliary epithelial cells undergo apoptosis, leading to degeneration of the intrahepatic biliary network. Consequently, in snapc4 mutant larvae, biliary transport of ingested fluorescent lipids to the gallbladder is blocked. Snapc4 is the largest subunit of a protein complex that regulates small nuclear RNA (snRNA) transcription. The snapc4(s445) mutation causes a truncation of the C-terminus, thereby deleting the domain responsible for a specific interaction with Snapc2, a vertebrate specific subunit of the SNAP complex. This mutation leads to a hypomorphic phenotype, as only a subset of snRNA transcripts are quantitatively altered in snapc4(s445) mutant larvae. snapc2 knockdown also disrupts the intrahepatic biliary network in a similar fashion as in snapc4(s445) mutant larvae. These data indicate that the physical interaction between Snapc2 and Snapc4 is important for the expression of a subset of snRNAs and biliary epithelial cell survival in zebrafish.
Authors:
Madeline Schaub; Justin Nussbaum; Heather Verkade; Elke A Ober; Didier Y R Stainier; Takuya F Sakaguchi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-23
Journal Detail:
Title:  Developmental biology     Volume:  363     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-16     Completed Date:  2012-05-21     Revised Date:  2013-07-18    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  128-37     Citation Subset:  IM    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Affiliation:
Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Genetically Modified
Binding Sites / genetics
Epithelial Cells / metabolism,  ultrastructure
Female
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Gene Regulatory Networks
Green Fluorescent Proteins / genetics,  metabolism
Immunohistochemistry
In Situ Hybridization
Larva / genetics,  growth & development,  metabolism
Liver / cytology,  growth & development,  metabolism*
Male
Microscopy, Confocal
Microscopy, Electron
Mutation*
Protein Binding
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Transcription Factors / genetics*,  metabolism
Zebrafish / genetics*,  growth & development,  metabolism
Zebrafish Proteins / genetics*,  metabolism
Grant Support
ID/Acronym/Agency:
DK078138/DK/NIDDK NIH HHS; R00 DK078138/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Snapc4 protein, zebrafish; 0/Transcription Factors; 0/Zebrafish Proteins; 147336-22-9/Green Fluorescent Proteins
Comments/Corrections

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


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