A transgenic zebrafish model of hepatocyte function in human Z α1-antitrypsin deficiency.
Biol Chem
; 400(12): 1603-1616, 2019 11 26.
Article
in En
| MEDLINE
| ID: mdl-31091192
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Alpha 1-Antitrypsin
/
Alpha 1-Antitrypsin Deficiency
/
Hepatocytes
/
Models, Animal
Limits:
Animals
/
Humans
Language:
En
Year:
2019
Type:
Article