{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:54:17Z","timestamp":1791348857625,"version":"4.3.1"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,4,21]],"date-time":"2017-04-21T00:00:00Z","timestamp":1492732800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,4,21]],"date-time":"2017-04-21T00:00:00Z","timestamp":1492732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 <jats:italic>in vitro<\/jats:italic>. 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 <jats:italic>in vivo<\/jats:italic> experiments. When W31X was studied in the human receptor, its superior read-through susceptibility \u2013 initially observed in the mouse receptor \u2013 was eliminated, likely due to the different nucleotide context surrounding the mutation in the two orthologues. The impact of the surrounding context on the read-through opens the possibility to discover novel sequence elements influencing nonsense suppression. As an alternative to toxic aminoglycosides, PTC124 was indicated as a superior nonsense suppressor but inconsistent data concerning its read-through activity are reported. PTC124 failed to rescue W31X as well as different nonsense mutated luciferase reporters, thus, challenging its ability to induce translational read-through.<\/jats:p>","DOI":"10.1038\/s41598-017-01093-9","type":"journal-article","created":{"date-parts":[[2017,4,13]],"date-time":"2017-04-13T10:35:05Z","timestamp":1492079705000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Aminoglycosides, but not PTC124 (Ataluren), rescue nonsense mutations in the leptin receptor and in luciferase reporter genes"],"prefix":"10.1038","volume":"7","author":[{"given":"Florian","family":"Bolze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Mocek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Klingenspor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,21]]},"reference":[{"key":"1093_CR1","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/humu.1380040302","volume":"4","author":"Population variation of common cystic fibrosis mutations","year":"1994","unstructured":"Population variation of common cystic fibrosis mutations. The Cystic Fibrosis Genetic Analysis Consortium. Population variation of common cystic fibrosis mutations. The Cystic Fibrosis Genetic Analysis Consortium. Hum. Mutat. \n                           4, 167\u2013177, doi:10.1002\/humu.1380040302 (1994).","journal-title":"Hum. Mutat."},{"key":"1093_CR2","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1002\/ajmg.1320570107","volume":"57","author":"TW Prior","year":"1995","unstructured":"Prior, T. W. et al. Spectrum of small mutations in the dystrophin coding region. Am. J. Hum. Genet. \n                           57, 22\u201333 (1995).","journal-title":"Am. J. Hum. Genet."},{"key":"1093_CR3","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.ymgmr.2014.10.002","volume":"1","author":"I Mazen","year":"2014","unstructured":"Mazen, I., Amr, K., Tantawy, S., Farooqi, I. S. & El Gammal, M. A novel mutation in the leptin gene (W121X) in an Egyptian family. Mol. Genet. Metab. 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