A new cellular model to follow Friedreich's ataxia development in a time-resolved way.
Friedreich's ataxia (FRDA) is a recessive autosomal ataxia caused by reduced levels of frataxin (FXN), an essential mitochondrial protein that is highly conserved from bacteria to primates. The exact role of frataxin and its primary function remain unclear although this information would be very valuable to design a therapeutic approach for FRDA. A main difficulty encountered so far has been that of establishing a clear temporal relationship between the different observations that could allow a distinction between causes and secondary effects, and provide a clear link between aging and disease development. To approach this problem, we developed a cellular model in which we can switch off/on in a time-controlled way the frataxin gene partially mimicking what happens in the disease. We exploited the TALEN and CRISPR methodologies to engineer a cell line where the presence of an exogenous, inducible FXN gene rescues the cells from the knockout of the two endogenous FXN genes. This system allows the possibility of testing the progression of disease and is a valuable tool for following the phenotype with different newly acquired markers.
['Vannocci|Tommaso|T|', 'Faggianelli|Nathalie|N|', 'Zaccagnino|Silvia|S|', 'della Rosa|Ilaria|I|', 'Adinolfi|Salvatore|S|', 'Pastore|Annalisa|A|']
D001483:Base Sequence D002460:Cell Line D064112:Clustered Regularly Interspaced Short Palindromic Repeats D004247:DNA D018450:Disease Progression D005621:Friedreich Ataxia D055786:Gene Knockout Techniques D005818:Genetic Engineering D057809:HEK293 Cells D006801:Humans D033862:Iron-Binding Proteins D008957:Models, Genetic D008969:Molecular Sequence Data D014162:Transfection
Cellular model Frataxin Disease development Genetic models Zinc fingers