Aminoglycosides, but not PTC124 (Ataluren), rescue nonsense mutations in the leptin receptor and in luciferase reporter genes.

ABSTRACT: In rare cases, monogenetic obesity is caused by nonsense mutations in genes regulating energy balance. A key factor herein is the leptin receptor. Here, we focus on leptin receptor nonsense variants causing obesity, namely the human W31X, murine Y333X and rat Y763X mutations, and explored their susceptibilities to aminoglycoside and PTC124 mediated translational read-through in vitro. In a luciferase based assay, all mutations - when analysed within the mouse receptor - were prone to aminoglycoside mediated nonsense suppression with the highest susceptibility for W31X, followed by Y763X and Y333X. For the latter, the corresponding rodent models appear valuable for in vivo experiments. When W31X was studied in the human receptor, its superior read-through susceptibility - initially observed

SUBMITTER: Bolze F 

PROVIDER: S-EPMC5430635 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature