A multi-omics approach reveals impaired lipid metabolism and oxidative stress in a zebrafish model of Alexander disease.

ABSTRACT: Alexander disease (AxD) is a rare leukodystrophy caused by heterozygous mutations in the GFAP gene. To date, several in vitro and in vivo models have been generated in an attempt to unravel the main mechanisms underlying this complex disease. However, none of these models is suitable for investigating the global dysregulation caused by AxD. To address this shortcoming, we have generated a stable transgenic zebrafish line (zAxD) carrying the human GFAP p.R239C mutation, which is associated with severe phenotypes of AxD type I patients. We then performed transcriptomics and proteomics analyses on the whole larvae of our zAxD model, confirming the involvement of several pathways such as the immune system response and inflammation, oxidative stress, extracellular matrix, lipoxidation and lipid

SUBMITTER: Bellitto D 

PROVIDER: S-EPMC11915002 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature