Deciphering the Effects of Frataxin Deficiency During Embryogenesis

Friedreich’s Ataxia (FRDA) is caused by an exonic GAA repeat expansion mutation that reduces the expression of the mitochondrial protein Frataxin (FXN). It is thought that this results in metabolic dysregulation and the accumulation of reactive oxygen species (ROS). However, important questions remain, specifically concerning FXN’s roles during embryonic development. We used morpholinos and CRISPR/Cas9 to study the effects of Fxn deficiency on embryogenesis. fxn-deficient zebrafish in both genetic models have increased cell death in the central nervous system. Additionally, both models have stunted renal development and reduced kidney function, though it was more severe in the morphant model. These studies demonstrate that Fxn is essential for the morphogenesis of several embryonic tissues. This new model has the potential to help identify novel treatments for FRDA.