Deletion of interleukin enhancer binding factor 2 (ILF2) resulted in defective biliary development and bile flow blockage
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In brief
In brief
Zebrafish knockout study demonstrates that deletion of ILF2 gene causes defective bile duct development and blocked bile flow, mirroring biliary atresia phenotypes. This is the first functional validation of BA-associated copy number variants, establishing ILF2 as a candidate gene in BA pathogenesis with potential diagnostic implications.
Written by the GCMD Library team from the article.
Abstract
Purpose
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.
Methods
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.
Results
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.
Conclusions
Such functional study may reveal the potential value of these BA-private CNVs in the disease pathogenesis for BA.
Level of evidence
N/A (animal and laboratory study).