A transgenic zebrafish model of hepatocyte function in human Z α1-antitrypsin deficiency
Author:
Yip Evelyn1, Giousoh Aminah1, Fung Connie1, Wilding Brendan1, Prakash Monica D.1, Williams Caitlin2, Verkade Heather3, Bryson-Richardson Robert J.2, Bird Phillip I.1
Affiliation:
1. Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute , Monash University , Melbourne 3800, Victoria , Australia 2. School of Biological Sciences , Monash University , Melbourne 3800, Victoria , Australia 3. Department of Biochemistry and Molecular Biology , University of Melbourne , Parkville 3052, Victoria , Australia
Abstract
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.
Publisher
Walter de Gruyter GmbH
Subject
Clinical Biochemistry,Molecular Biology,Biochemistry
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