Readthrough of dystrophin stop codon mutations induced by aminoglycosides.
We report the translational readthrough levels induced by the aminoglycosides gentamicin, amikacin, tobramycin, and paromomycin for eight premature stop codon mutations identified in Duchenne's and Becker's muscular dystrophy patients. In a transient transfection reporter assay, aminoglycoside treatment results show that one stop codon mutation is suppressed significantly better (up to 10% stop codon readthrough) than the others; five show lower but statistically significant suppression (< 2% stop codon readthrough); and two appear refractory to aminoglycoside treatment. Readthrough levels do not substantially vary between different sources of gentamicin, and, for this set of mutations, the efficiency of termination at the premature stop codon mutation does not appear to correlate with disease severity.
Howard
Michael T
MT
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
Anderson
Christine B
CB
Fass
Uwe
U
Khatri
Shikha
S
Gesteland
Raymond F
RF
Atkins
John F
JF
Flanigan
Kevin M
KM
D000617:Aminoglycosides / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018389:Codon, Nonsense / Q000187:drug effects; D018388:Codon, Terminator / Q000187:drug effects*; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D016189:Dystrophin / Q000235:genetics*; D004622:Embryo, Mammalian; D006801:Humans; D007668:Kidney; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation / Q000187:drug effects*; D032446:Myoblasts / Q000187:drug effects; D004364:Pharmaceutical Preparations; D014176:Protein Biosynthesis / Q000187:drug effects; D016364:Reading Frames; D014162:Transfection
D000617:Aminoglycosides; D018389:Codon, Nonsense; D018388:Codon, Terminator; D016189:Dystrophin; D004364:Pharmaceutical Preparations; D008156:Luciferases