Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations
Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations
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DOI：
10.1038/nm0496-467
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发表时间：
1996-04-01
期刊：
影响因子：
82.9
通讯作者：
Bedwell, DM
中科院分区：
文献类型：
--
作者：
Howard, M;Frizzell, DM;Bedwell, DM
囊性纤维化（CF）是由编码CF跨膜传导调节因子（CFTR）的基因突变引起的。苯丙氨酸508 （Delta F508）的单隐性突变缺失会导致严重的CF，并存在于70%的突变染色体上。严重的CF也由过早停止突变引起，这种突变在5%的CF染色体上发现。在这里，我们报告了两种常见的疾病相关的停止突变可以通过使用低剂量的氨基糖苷类抗生素G-418治疗细胞来抑制。氨基糖苷处理导致全长CFTR的表达，并恢复其环amp激活的氯通道活性。另一种氨基糖苷庆大霉素也能促进全长CFTR的表达。这些结果表明，氨基糖苷类治疗可能提供了一种恢复CFTR功能的方法，用于CF患者的这类突变。
Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR). A single recessive mutation, the deletion of phenylalanine 508 (Delta F508), causes severe CF and resides on 70% of mutant chromosomes. Severe CF is also caused by premature stop mutations, which are found on 5% of CF chromosomes. Here we report that two common, disease-associated stop mutations can be suppressed by treating cells with low doses of the aminoglycoside antibiotic G-418. Aminoglycoside treatment resulted in the expression of full-length CFTR and restored its cyclic AMP-activated chloride channel activity. Another aminoglycoside, gentamicin, also promoted the expression of full-length CFTR. These results suggest that treatment with aminoglycosides may provide a means of restoring CFTR function in CF patients with this class of mutation.