A new cellular model to follow Friedreich's ataxia development in a time-resolved way

Disease Models & Mechanisms

Annalisa Pastore¹  Salvatore Adinolfi¹  Tommaso Vannocci²  Nathalie Faggianelli²  Silvia Zaccagnino²  Ilaria della Rosa² 

[1] Department of Basic and Clinical Neurosciences, Kings College London, London NW7 1AA, UK;Molecular Structure Division, MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK;

关键词: Cellular model;    Disease development;    Frataxin;    Genetic models;    Zinc fingers;   

DOI  :  10.1242/dmm.020545

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown