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Transcriptional profiling of mouse embryonic fibroblasts harboring the Fxn G127V mutation

GSE255810 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/01/22 Platform GPL24247
Summary
Friedreich's ataxia (FRDA) is a neurodegenerative disease caused by mutations in the frataxin (FXN) gene. In this study, we immortalized mouse embryonic fibroblasts (MEFs) derived from G127V Fxn mutant mice and compared them to the wild-type (WT) MEFs. Mutant G127V MEFs demonstrated decreased cell proliferation and ATP production, as well as an increase in reactive oxygen species (ROS) production when compared to WT cells. These phenotypes are partially corrected by exogenous expression of frataxin. Surprisingly, extended passaging of immortalized G127V Fxn MEFs improves their proliferation, and alleviates ATP deficiency as well as decreases ROS levels despite persistent frataxin deficiency. We defined gene expression changes associated with phenotypic adaptation of G127V mutant MEFs by comparing transcriptional profiles of early and late passage G127V MEFs with WT cells.
Published in
Design and validation of cell-based potency assays for frataxin supplementation treatments
Mukherjee S, Pereboeva L, Fil D et al. · Molecular therapy. Methods & clinical development 2024 · PMID 39823061 · doi:10.1016/j.omtm.2024.101347
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Also filed as BioProject PRJNA1076569 and SRA study SRP491503. Searching any of these in the dataset finder brings you back here.

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