PUBLICATION

Mutation of zebrafish Snapc4 is associated with loss of the intrahepatic biliary network

Authors
Schaub, M., Nussbaum, J., Verkade, H., Ober, E.A., Stainier, D.Y., and Sakaguchi, T.F.
ID
ZDB-PUB-120111-24
Date
2012
Source
Developmental Biology   363(1): 128-137 (Journal)
Registered Authors
Ober, Elke, Sakaguchi, Takuya, Schaub, Madeline, Stainier, Didier, Verkade, Heather
Keywords
liver, snRNA, SNAP190, SNAPC2, biliary epithelial cells, vanishing bile duct
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Binding Sites/genetics
  • Epithelial Cells/metabolism
  • Epithelial Cells/ultrastructure
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Gene Regulatory Networks
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Larva/genetics
  • Larva/growth & development
  • Larva/metabolism
  • Liver/cytology
  • Liver/growth & development
  • Liver/metabolism*
  • Male
  • Microscopy, Confocal
  • Microscopy, Electron
  • Mutation*
  • Protein Binding
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transcription Factors/genetics*
  • Transcription Factors/metabolism
  • Zebrafish/genetics*
  • Zebrafish/growth & development
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
22222761 Full text @ Dev. Biol.
Abstract

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, the biliary epithelial cells undergo apoptosis, leading to the 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 the protein complex that regulates small nuclear RNA (snRNA) transcription. The snapc4s445 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 snapc4s445 mutant larvae. snapc2 knockdown also disrupts the intrahepatic biliary network in a similar fashion as in snapc4s445 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.

Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes