Abstract | BACKGROUND: METHODS: RESULTS:
G418 treatment induced translational readthrough of CTNSW138X constructs transfected into HEK293 cells and expression of full-length endogenous CTNS protein in homozygous W138X fibroblasts. CONCLUSIONS: Reduction in intracellular cystine indicates that the CTNS protein produced is functional as a cystine transporter. Interestingly, similar effects were seen even in W138X compound heterozygotes. These studies establish proof-of-principle for the potential of aminoglycosides to treat cystinosis and possibly other monogenic diseases caused by nonsense mutations.
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Authors | Emma J Brasell, LeeLee Chu, Reyhan El Kares, Jung Hwa Seo, Robin Loesch, Diana M Iglesias, Paul Goodyer |
Journal | Pediatric nephrology (Berlin, Germany)
(Pediatr Nephrol)
Vol. 34
Issue 5
Pg. 873-881
(05 2019)
ISSN: 1432-198X [Electronic] Germany |
PMID | 30413946
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amino Acid Transport Systems, Neutral
- CTNS protein, human
- Codon, Nonsense
- Gentamicins
- RNA, Messenger
- Recombinant Proteins
- Cystine
- antibiotic G 418
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Topics |
- Amino Acid Transport Systems, Neutral
(genetics)
- Codon, Nonsense
- Cystine
(metabolism)
- Cystinosis
(drug therapy, genetics)
- Fibroblasts
(drug effects, metabolism)
- Genetic Vectors
(genetics)
- Gentamicins
(pharmacology, therapeutic use)
- HEK293 Cells
- Humans
- Peptide Chain Termination, Translational
(drug effects, genetics)
- Plasmids
(genetics)
- RNA, Messenger
(analysis)
- Recombinant Proteins
(genetics)
- Transfection
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