C. elegans has many orthologues of human genes including many genes involved in human disease. This feature allows the use of this worm as a model organism for biomedical research. Our aim in the present work is to establish a C. elegans model to study the pathophysiology of the Friedreichs ataxia. Friedreich's ataxia is an autosomal recessive neurodegenerative disease caused by mutations in the FRDA gene. The most frequent mutation is the expansion of a GAA triplet, which prevents correct transcription. This leads to a decrease in the level of frataxin, the product of this gene. This results in ataxic movements, sensory axonal neuropathy, cardiomyopathy, skeletal deformities, and diabetes mellitus or glucose intolerance. Frataxin is localized in the inner membrane of mitochondria. Lack of yeast frataxin, Yfh1p, produces an increase in mitochondrial iron, increased sensitivity to oxidative stress, and respiration deficiency. Iron-sulphur cluster biogenesis also seems to be affected.We describe the expression pattern of the C. elegans FRDA orthologue,
frh-1 (F59G1.7). To elucidate the expression pattern of the nematode frataxin we generated transgenic lines by injecting a number of
frh-1::gfp constructs differing in the size of the 5' fragments of genomic DNA wich they contained.
frh-1 is expressed in specific head neurons, muscles, pharynx and intestine. This tissue pattern shows some analogy to human histological expression of frataxin.Transient knock-down experiments by RNAi produce a specific phenotype in worms of the F1 generation. The worms are: thin and short, Egl, have slow and arrhythmic pharynx pumping, and an increase in the period of the defecation rhythm. This model may be useful not only for studying pathogenic mechanisms of frataxin deficiency but also for drug screening.