Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong.
Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong; Dr. Li Dak-Sum Research Centre, The University of Hong Kong-Karolinska Institutet Collaboration in Regenerative Medicine, 5/F The Hong Kong Jockey Club Building for Interdisciplinary Research, The University of Hong Kong 5 Sassoon Road, Pokfulam, Hong Kong.
J Pediatr Surg. 2021 Feb;56(2):352-359. doi: 10.1016/j.jpedsurg.2020.06.032. Epub 2020 Jun 27.
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).
先天性胆道闭锁（BA）是一种毁灭性的新生儿阻塞性胆管疾病。BA 在亚洲人中的发病率最高（1/5000），其发病机制尚不清楚。我们鉴定出 BA 特有的罕见拷贝数变异（CNVs；22 个重复和 6 个缺失）。ILF2 基因位于染色体区域（Chr1：153410347-153634058），该区域在一名非综合征性 BA 患者中缺失。然而，目前尚不清楚 ILF2 是否在肝胆发育中发挥作用，以及其缺失是否会影响胆管发育。
为了研究 ILF2 是否是胆管发育所必需的，我们通过 CRISPR/Cas9 方法敲除了斑马鱼的 ILF2 同源物，并发现 ILF2 的缺失导致斑马鱼的胆管发育缺陷和胆汁从肝脏到胆囊的流动缺失，这与 BA 的表型相似。
我们的数据表明，ILF2 基因是胆管发育所必需的；ILF2 的缺失会损害胆管发育，并可能导致 BA 的发病机制。这将是首次对 BA 特有的 CNVs 干扰的基因在肝胆发育和 BA 发病机制中的功能进行评估。
这种功能研究可能揭示了这些 BA 特有的 CNVs 在 BA 发病机制中的潜在价值。
N/A（动物和实验室研究）。
