Neb: a zebrafish model of nemaline myopathy due to nebulin mutation.
Neb: a zebrafish model of nemaline myopathy due to nebulin mutation.
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DOI：
10.1242/dmm.008631
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发表时间：
2012-05
影响因子：
4.3
通讯作者：
Dowling JJ
中科院分区：
文献类型：
--
作者：
Telfer WR;Nelson DD;Waugh T;Brooks SV;Dowling JJ
线状肌病是儿童最常见和严重的非营养不良性肌肉疾病之一。患者通常在婴儿期表现为张力低下、虚弱、运动发育迟缓、球和呼吸困难。六种不同基因的突变与线状肌病有关，其中星云蛋白突变是最常见的。目前还没有针对这种疾病的治疗方法或疾病改善疗法。治疗发展的主要障碍之一是缺乏对潜在治疗策略进行快速和协调测试的模型。为了克服这一障碍，我们描述了第一个斑马鱼的线状肌病模型。这种模型，被称为neb，在星云蛋白基因中含有隐性突变，导致星云蛋白水平降低，严重的运动表型和过早死亡。除了运动功能受损外，斑马鱼还表现出许多与人类线状肌病相关的特征。这些包括产生力受损，细丝长度改变和特定组织病理学变化的存在，包括线状体的形成。总之，neb斑马鱼反映了neb突变引起的线状肌病的遗传、临床和病理方面，因此是未来治疗这种毁灭性疾病的良好模型。
Nemaline myopathy is one of the most common and severe non-dystrophic muscle diseases of childhood. Patients typically present in infancy with hypotonia, weakness, delayed motor development, and bulbar and respiratory difficulties. Mutations in six different genes are associated with nemaline myopathy, with nebulin mutations being the most common. No treatments or disease-modifying therapies have been identified for this disease. One of the major barriers to treatment development is the lack of models amenable to rapid and coordinated testing of potential therapeutic strategies. To overcome this barrier, we have characterized the first zebrafish model of nemaline myopathy. This model, termed neb, harbors a recessive mutation in the nebulin gene that results in decreased Nebulin protein levels, a severe motor phenotype and premature lethality. In addition to impaired motor function, neb zebrafish exhibit many of the features associated with human nemaline myopathy. These include impaired force generation, altered thin filament length and the presence of specific histopathological changes, including the formation of nemaline bodies. In summary, neb zebrafish mirror the genetic, clinical and pathological aspects of nemaline myopathy due to NEB mutation, and thus are an excellent model for future therapy development for this devastating disorder.
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影响因子：
4.5
作者：
Dowling, James J.;Vreede, Andrew P.;Low, Sean E.;Gibbs, Elizabeth M.;Kuwada, John Y.;Bonnemann, Carsten G.;Feldman, Eva L.
通讯作者：
Feldman, Eva L.
影响因子：
2.8
作者：
Darin, N;Tulinius, M
通讯作者：
Tulinius, M
影响因子：
4.8
作者：
Jin, JP;Brotto, MA;Crawford, TO
通讯作者：
Crawford, TO
影响因子：
4.8
作者：
Chandra, Murali;Mamidi, Ranganath;Granzier, Henk
通讯作者：
Granzier, Henk
影响因子：
3.5
作者：
Ottenheijm, Coen A. C.;Witt, Christian C.;Granzier, Henk
通讯作者：
Granzier, Henk