Ribosomal protein gene knockdown causes developmental defects in zebrafish.
Ribosomal protein gene knockdown causes developmental defects in zebrafish.
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核糖体蛋白基因敲低导致斑马鱼的发育缺陷。
DOI：
10.1371/journal.pone.0000037
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发表时间：
2006-12-20
期刊：
影响因子：
3.7
通讯作者：
Kenmochi, Naoya
中科院分区：
文献类型：
--
作者：
Uechi, Tamayo;Nakajima, Yukari;Nakao, Akihiro;Torihara, Hidetsugu;Chakraborty, Anirban;Inoue, Kunio;Kenmochi, Naoya
核糖体蛋白（RPs）形成大多数细胞蛋白，并且对于细胞生长是必需的。RP基因直接或间接地与人类的各种疾病有关。RP基因的突变也与组织特异性表型相关，这表明在早期胚胎发生过程中可能在器官发育中发挥作用。然而，目前还不知道特定RP基因的突变如何导致特定的细胞变化，或者RP基因如何导致人类疾病。RP基因缺陷动物模型的建立对研究这些问题至关重要。在本研究中，我们敲低21 RP基因的斑马鱼，通过使用吗啉代反义寡核苷酸抑制其翻译。在这21个中，敲低19个RP导致了具有明显畸形的morphants的发展。虽然RP基因的突变，像其他管家基因，预计会导致非特异性发育缺陷与广泛的表型，我们发现，一些RP基因的敲除导致表型特定于每个基因，不同程度的异常，在大脑，躯干，眼睛和耳朵在受精后约25小时。我们进一步关注大脑的器官发生。每一个影响大脑形态发生的被敲低的基因都会产生不同的异常模式。在敲低产生严重脑表型的7个RP基因中，3个人类直系同源物位于与脑相关疾病相关的染色体区域内，表明RP基因可能参与脑或神经系统疾病。本研究建立的RP基因敲除系统为研究核糖体在人类疾病中的作用提供了有力的工具。
The ribosomal proteins (RPs) form the majority of cellular proteins and are mandatory for cellular growth. RP genes have been linked, either directly or indirectly, to various diseases in humans. Mutations in RP genes are also associated with tissue-specific phenotypes, suggesting a possible role in organ development during early embryogenesis. However, it is not yet known how mutations in a particular RP gene result in specific cellular changes, or how RP genes might contribute to human diseases. The development of animal models with defects in RP genes will be essential for studying these questions. In this study, we knocked down 21 RP genes in zebrafish by using morpholino antisense oligos to inhibit their translation. Of these 21, knockdown of 19 RPs resulted in the development of morphants with obvious deformities. Although mutations in RP genes, like other housekeeping genes, would be expected to result in nonspecific developmental defects with widespread phenotypes, we found that knockdown of some RP genes resulted in phenotypes specific to each gene, with varying degrees of abnormality in the brain, body trunk, eyes, and ears at about 25 hours post fertilization. We focused further on the organogenesis of the brain. Each knocked-down gene that affected the morphogenesis of the brain produced a different pattern of abnormality. Among the 7 RP genes whose knockdown produced severe brain phenotypes, 3 human orthologs are located within chromosomal regions that have been linked to brain-associated diseases, suggesting a possible involvement of RP genes in brain or neurological diseases. The RP gene knockdown system developed in this study could be a powerful tool for studying the roles of ribosomes in human diseases.
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影响因子：
4.4
作者：
Uechi, T;Tanaka, T;Kenmochi, N
通讯作者：
Kenmochi, N
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5.3
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Matsson, H;Davey, EJ;Dahl, N
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Irobi, J;Van Impe, K;Timmerman, V
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Timmerman, V
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Tang, BS;Zhao, GH;Dai, HP
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作者：
Yoshihama, M;Uechi, T;Kenmochi, N
通讯作者：
Kenmochi, N