A novel reporter system to investigate the molecular cause of Friedreich Ataxia

• DOI: 10.1096/fasebj.22.1_supplement.781.1
• Publication Date: 2021-06-21T23:32:29Z
• Authors: Ayan Banerjee; Scott Ditch; Mimi C. Sammarco; Ed Grabczyk
• Keywords: Frataxin; Transcription

Friedreich ataxia (FRDA), is a neurodegenerative disease accompanied by hypertrophic cardiomyopathy. FRDA patients suffer an unrelenting progressive and most eventually succumb to cardiac failure. Most are homozygous for large GAA•TTC repeat expansions in the intron 1 of FXN gene. Disease severity directly correlates size expansion, which represses gene expression mechanism that still unclear. In order investigate this inhibition expanded repeats, we designed splicing minigene construct carrying two reporters under control bi‐directional tetracycline inducible promoter. We then used Invitrogen Flp‐In system integrate our constructs repeats varying sizes into unique chromosomal location cell lines. Surprisingly, as 352 do not cause decreased transcription system. However, lengths between 700–1000 showed marked inhibition, suggesting larger threshold than presently believed. using tool better define possible role co‐transcriptional events inhibition. These lines will also serve high throughput assay testing therapeutic interventions. This work was supported NIH grant number R01NS046567 from Friedreich's Ataxia Research Alliance (FARA).