Russi M, Martin E, D'Autréaux B, Tixier L, Tricoire H, Monnier V. A Drosophila model of Friedreich Ataxia with CRISPR/Cas9 insertion of GAA repeats in the frataxin gene reveals in vivo protection by N-acetyl cysteine. Hum Mol Genet. 2020 Aug 3:ddaa170. doi: 10.1093/hmg/ddaa170. Epub ahead of print. PMID: 32744307.
From the abstract:
"Friedreich Ataxia (FA) is caused by GAA repeat expansions in the first intron of FXN, the gene encoding frataxin, which results in decreased gene expression. ... Drosophila melanogaster fruitfly appears as an adequate animal model to study this disease ... Here, we generated a Drosophila model of FA with CRISPR/Cas9 insertion of approximately 200 GAA in the intron of the fly frataxin gene fh. ... We were able to by-pass preadult lethality ... These frataxin-deficient adults are short-lived and present strong locomotor defects. RNA-Seq analysis identified deregulation of genes involved in amino-acid metabolism and transcriptomic signatures of oxidative stress. In particular, we observed a progressive increase of Tspo expression, fully rescued by adult frataxin expression. Thus, Tspo expression constitutes a molecular marker of the disease progression in our fly model and might be of interest in other animal models or in patients. Finally, in a candidate drug screening, we observed that N-acetyl cysteine improved the survival, locomotor function, resistance to oxidative stress and aconitase activity of frataxin-deficient flies. ..."
No comments:
Post a Comment