PUBLICATION

Deletion of interleukin enhancer binding factor 2 (ILF2) resulted in defective biliary development and bile flow blockage

Authors
Cheung, Y., Wu, Z., Garcia-Barcelo, M.M., Tam, P.K.H., Ma, A.C.H., Lui, V.C.H.
ID
ZDB-PUB-200728-16
Date
2020
Source
Journal of Pediatric Surgery   56(2): 352-359 (Journal)
Registered Authors
Keywords
Bile duct, Biliary atresia, ILF2, Liver, Zebrafish
MeSH Terms
  • Animals
  • Bile
  • Bile Ducts
  • Biliary Atresia*/genetics
  • Humans
  • Infant, Newborn
  • Nuclear Factor 45 Protein
  • Zebrafish*/genetics
PubMed
32709532 Full text @ J. Pediatr. Surg.
Abstract
Biliary atresia (BA) is a devastating obstructive bile duct disease of newborns. BA has the highest incidence in Asians (1/5000), and its pathogenesis is unclear. We identified BA-private rare copy number variants (CNVs; 22 duplications and 6 deletions). ILF2 gene locates in the chromosome region (Chr1:153410347-153,634,058) which was deleted in a nonsyndromic BA patient. However, it is still not known whether ILF2 plays a role in hepatobiliary development and its deletion impacts on the bile duct development.
To investigate if ILF2 is required for biliary development, we knock-out the zebrafish homologs of ILF2 by CRISPR/Cas9 approach, and discover that deletion of ILF2 causes a defective biliary development and a lack of bile flow from the liver to the gall bladder in zebrafish, which is a resemblance of phenotypes of BA.
Our data indicate that ILF2 gene is required for biliary development; deletion of ILF2 impairs bile duct development and could contribute to BA pathogenesis. This will be the first study to functionally evaluate the genes interfered by BA-private CNVs in hepatobiliary development and in BA pathogenesis.
Such functional study may reveal the potential value of these BA-private CNVs in the disease pathogenesis for BA.
N/A (animal and laboratory study).
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping