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- Title
CRISPR/Cas9-based edition of frataxin gene in Dictyostelium discoideum.
- Authors
Gentili, Hernan G.; Pignataro, María Florencia; Olmos, Justo; Pavan, María Florencia; Itatí Ibañez, Lorena; Santos, Javier; Velazquez Duarte, Francisco
- Abstract
In this paper, we describe the development of a Dictyostelium discoideum strain deficient in frataxin protein (FXN). We investigated the conservation of function between humans and D. discoideum and showed that DdFXN can substitute the human version in the interaction and activation of the Fe-S assembly supercomplex. We edited the D. discoideum fxn locus and isolated a defective mutant, clone 8, which presents landmarks of frataxin deficiency, such as a decrease in Fe-S cluster-dependent enzymatic functions, growth rate reduction, and increased sensitivity to oxidative stress. In addition, the multicellular development is affected as well as growing on bacterial lawn. We also assessed the rescuing capacity of DdFXN-G122V, a version that mimics a human variant present in some FA patients. While the expression of DdFXN-G122V rescues growth and enzymatic activity defects, as DdFXN does, multicellular development defects were only partially rescued. The results of the study suggest that this new D. discoideum strain offers a wide range of possibilities to easily explore diverse FA FXN variants. This can facilitate the development of straightforward drug screenings to look for new therapeutic strategies.
- Subjects
DICTYOSTELIUM discoideum; FRATAXIN; CRISPRS; OXIDATIVE stress; DRUG development
- Publication
Biochemical Journal, 2023, Vol 480, Issue 19, p1533
- ISSN
0264-6021
- Publication type
Article
- DOI
10.1042/BCJ20230244