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- Title
A flow cytometry-based reporter assay identifies macrolide antibiotics as nonsense mutation read-through agents.
- Authors
Caspi, Michal; Firsow, Anastasia; Rajkumar, Raja; Skalka, Nir; Moshkovitz, Itay; Munitz, Ariel; Pasmanik-Chor, Metsada; Greif, Hagar; Megido, Dalia; Kariv, Revital; Rosenberg, Daniel; Rosin-Arbesfeld, Rina
- Abstract
A large number of human diseases are caused by nonsense mutations. These mutations result in premature protein termination and the expression of truncated, usually nonfunctional products. A promising therapeutic strategy for patients suffering from premature termination codon (PTC)-mediated disorders is to suppress the nonsense mutation and restore the expression of the affected protein. Such a suppression approach using specific antibiotics and other read-through promoting agents has been shown to suppress PTCs and restore the production of several important proteins. Here, we report the establishment of a novel, rapid, and very efficient method for screening stop-codon read-through agents. We also show that, in both mammalian cells and in a transgenic mouse model, distinct members of the macrolide antibiotic family can induce read-through of disease-causing stop codons leading to re-expression of several key proteins and to reduced disease phenotypes. Taken together, our results may help in the identification and characterization of well-needed customized pharmaceutical PTC suppression agents. Key messages:
- Subjects
CYTOMETRY; ALLELOPATHIC agents; PHYTONCIDES; MACROCYCLIC compounds; GENETIC mutation
- Publication
Journal of Molecular Medicine, 2016, Vol 94, Issue 4, p469
- ISSN
0946-2716
- Publication type
Article
- DOI
10.1007/s00109-015-1364-1