A promising mouse model for Friedreich Ataxia progressing like human patients

Friedreich Ataxia (FRDA) is a genetic disease caused by an expended GAA repeat in the FXN gene leading to a reduction in frataxin protein production. Frataxin is an essential protein involved in mitochondrial iron-sulfur-cluster formation, its absence affecting numerous cellular rections. In patients, the disease leads to a progressive neuromuscular degeneration and, most of the time, death from heart failure. In order to determine if a treatment is effective or not, it is essential to have the mouse model, which best reflects all of the characteristics of this disease. Many groups were working on the creation of mouse models by decreasing the mouse frataxin or knocking it out, by introducing a transgene with a human frataxin with long GAA repeat. Most of the mouse models are limited to one problem, either neurologic or cardiac symptoms, and, for those who have both, generally these symptoms are too severe and mice have a very short life span, which does not reflect the human disease's progression. Jackson Laboratories Inc. developed a new mouse model that has 800 GAA repeats. We demonstrate here that these mice accurately reflect the human disease with a progressive neuromuscular degeneration highlighted by the two beam tests and the beginning of heart hypertrophy at 26 weeks. YG8-800 mice are thus currently a promising mouse model for FRDA.