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

ABSTRACT 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. Summary: This paper describes the development of a new cellular model to study the neurodegenerative Friedreich's ataxia based on the use and development of new CRISPR and TALEN platforms.

• Publication year

  2015

• Venue

  Disease Models & Mechanisms

• Publication date

  2015-07-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1242/dmm.020545PMID 26035392PMCID 4486863
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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