Feeding difficulties, a key feature of the Drosophila NDUFS4 mitochondrial disease model.
Feeding difficulties, a key feature of the Drosophila NDUFS4 mitochondrial disease model.
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DOI：
10.1242/dmm.032482
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发表时间：
2018-03-27
影响因子：
4.3
通讯作者：
Smeitink JAM
中科院分区：
文献类型：
--
作者：
Foriel S;Beyrath J;Eidhof I;Rodenburg RJ;Schenck A;Smeitink JAM
线粒体疾病与各种各样的临床症状和不同程度的严重性相关。患有这类疾病的患者通常预后不良，并且通常具有早期致命的疾病结局。由于发病率为1/5000活产，并且没有可用的治愈性治疗，迫切需要相关的动物模型来评估线粒体疾病的新治疗方案。通过敲低ND-18，NDUFS 4的独特果蝇直系同源物，NADH的辅助亚基：泛醌氧化还原酶（复合物I），我们开发和表征了几个dNDUFS 4模型，概括了线粒体疾病的关键特征。与人类一样，dNDUFS 4 KD果蝇表现出严重的进食困难，这是迄今为止在动物模型中基本上被忽视的线粒体疾病的一个方面。这一发现的影响，以及克服它的方法，将在解释疾病模型表征和干预研究的背景下进行讨论。这篇文章有一个相关的第一人称采访的论文的第一作者。总结：NDUFS 4线粒体疾病的新果蝇模型的表征揭示了进食能力的明显缺陷，并概括了其他人类疾病特征。
Mitochondrial diseases are associated with a wide variety of clinical symptoms and variable degrees of severity. Patients with such diseases generally have a poor prognosis and often an early fatal disease outcome. With an incidence of 1 in 5000 live births and no curative treatments available, relevant animal models to evaluate new therapeutic regimes for mitochondrial diseases are urgently needed. By knocking down ND-18, the unique Drosophila ortholog of NDUFS4, an accessory subunit of the NADH:ubiquinone oxidoreductase (Complex I), we developed and characterized several dNDUFS4 models that recapitulate key features of mitochondrial disease. Like in humans, the dNDUFS4 KD flies display severe feeding difficulties, an aspect of mitochondrial disorders that has so far been largely ignored in animal models. The impact of this finding, and an approach to overcome it, will be discussed in the context of interpreting disease model characterization and intervention studies. This article has an associated First Person interview with the first author of the paper. Summary: The characterization of a novel Drosophila model of NDUFS4 mitochondrial disease revealed a pronounced defect in feeding abilities and recapitulated additional human disease features.
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DOI：
10.1073/pnas.0702726104
发表时间：
2007-05-15
影响因子：
11.1
作者：
Ja, William W.;Carvalho, Gil B.;Benzer, Seymour
通讯作者：
Benzer, Seymour
影响因子：
29
作者：
Guerrero-Castillo, Sergio;Baertling, Fabian;Nijtmans, Leo
通讯作者：
Nijtmans, Leo
影响因子：
8.8
作者：
Garcia CJ;Khajeh J;Coulanges E;Chen EI;Owusu-Ansah E
通讯作者：
Owusu-Ansah E
影响因子：
48
作者：
Deshpande, Sonali A.;Carvalho, Gil B.;Amador, Ariadna;Phillips, Angela M.;Hoxha, Sany;Lizotte, Keith J.;Ja, William W.
通讯作者：
Ja, William W.
影响因子：
1.2
作者：
Diegelmann, Soeren;Jansen, Annika;Scholz, Henrike
通讯作者：
Scholz, Henrike