A mouse model for nonsense mutation bypass therapy shows a dramatic multiday response to geneticin.
A mouse model for nonsense mutation bypass therapy shows a dramatic multiday response to geneticin.
复制标题
无义突变旁路疗法的小鼠模型显示出对遗传霉素的显着的多日反应。
DOI：
10.1073/pnas.0610878104
复制
发表时间：
2007
影响因子：
11.1
通讯作者：
Sommer,SteveS
中科院分区：
文献类型：
--
作者：
Yang,Chunmei;Feng,Jinong;Song,Wenjia;Wang,Jicheng;Tsai,Becky;Zhang,Yunwu;Scaringe,WilliamA;Hill,KathleenA;Margaritis,Paris;High,KatherineA;Sommer,SteveS
Aminoglycosides can bypass nonsense mutations and are the prototypic agents for translational bypass therapy (TBT). Initial results demonstrate the need for more potent drugs and anin vivomodel system for quantitative assessment of TBT. Herein, we present anin vivosystem for evaluating the efficacy of premature stop codon management therapies:in vivoquantitative stop codon management repli-sampling TBT efficacy assay (IQSCMaRTEA). Application of IQSCMaRTEA reveals that geneticin is much more efficaciousin vivothan gentamicin. Treatment with geneticin elicits a multiday response, and residualF9antigen can be detected after 3 weeks. These data demonstrate the utility of IQSCMaRTEA for evaluating drugs that bypass nonsense mutations. In addition, IQSCMaRTEA may be helpful for testing inhibitors of nonsense-mediated decay, as stop codon management therapy will sometimes require inhibition of nonsense-mediated decay and translational bypass of the nonsense mutation. Furthermore, geneticin, its metabolites, or better tolerated analogues should be evaluated as a general treatment with multiday response for severe genetic disease caused by nonsense mutation.
