Animal Models of Friedreich Ataxia

Friedreich ataxia (FRDA) is the most common form of autosomal-recessive ataxia. Common nonmotor features include cardiomyopathy and diabetes mellitus. At present, no effective treatments are available to prevent disease progression. Age of onset varies from infancy to adulthood. In the majority of patients, FRDA is caused by intronic GAA expansions in FXN, which encodes a highly-conserved small mitochondrial matrix protein, frataxin. A mouse model of FRDA has been difficult to generate because complete loss of frataxin causes early embryonic lethality. Although there are some controversies about the function of frataxin, recent biochemical and structural studies have confirmed that it is a component of the multiprotein complex that assembles iron-sulfur clusters in the mitochondrial matrix. The main consequences of frataxin deficiency are energy deficit, altered iron metabolism, and oxidative damage.