PUBLICATION

A transgenic zebrafish model of hepatocyte function in human Z α1-antitrypsin deficiency

Authors
Yip, E., Giousoh, A., Fung, C., Wilding, B., Prakash, M.D., Williams, C., Verkade, H., Bryson-Richardson, R.J., Bird, P.I.
ID
ZDB-PUB-190516-20
Date
2018
Source
Biological chemistry   400(12): 1603-1616 (Journal)
Registered Authors
Bird, Phillip I., Bryson-Richardson, Robert, Verkade, Heather
Keywords
Danio rerio, SERPINA1, liver, serpin, α1-antitrypsin deficiency
MeSH Terms
  • Animals
  • CHO Cells
  • Cell Line
  • Cricetulus
  • Hepatocytes/metabolism*
  • Humans
  • Models, Animal*
  • Mutation
  • Zebrafish
  • alpha 1-Antitrypsin/genetics
  • alpha 1-Antitrypsin/metabolism*
  • alpha 1-Antitrypsin Deficiency/genetics
  • alpha 1-Antitrypsin Deficiency/metabolism*
PubMed
31091192 Full text @ Biol. Chem.
Abstract
In human α1-antitrypsin deficiency, homozygous carriers of the Z (E324K) mutation in the gene SERPINA1 have insufficient circulating α1-antitrypsin and are predisposed to emphysema. Misfolding and accumulation of the mutant protein in hepatocytes also causes endoplasmic reticulum stress and underpins long term liver damage. Here we describe transgenic zebrafish (Danio rerio) expressing the wildtype or the Z mutant form of human α1- antitrypsin in hepatocytes. As observed in afflicted humans, and in rodent models, about 80% less α1-antitrypsin is evident in the circulation of zebrafish expressing the Z mutant. Although these zebrafish also show signs of liver stress they do not accumulate α1-antitrypsin in hepatocytes. This new zebrafish model will provide useful insights into understanding and treatment of α1-antitrypsin deficiency.
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