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- Title
A transgenic zebrafish model of hepatocyte function in human Z α1-antitrypsin deficiency.
- Authors
Yip, Evelyn; Giousoh, Aminah; Fung, Connie; Wilding, Brendan; Prakash, Monica D.; Williams, Caitlin; Verkade, Heather; Bryson-Richardson, Robert J.; Bird, Phillip I.
- 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.
- Subjects
ZEBRA danio; ENDOPLASMIC reticulum; MUTANT proteins; BRACHYDANIO; LIVER
- Publication
Biological Chemistry, 2019, Vol 400, Issue 12, p1603
- ISSN
1431-6730
- Publication type
Article
- DOI
10.1515/hsz-2018-0391