Migration defects by DISC1 knockdown in C57BL/6, 129X1/SvJ, and ICR strains via in utero gene transfer and virus-mediated RNAi.
Migration defects by DISC1 knockdown in C57BL/6, 129X1/SvJ, and ICR strains via in utero gene transfer and virus-mediated RNAi.
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DOI：
10.1016/j.bbrc.2010.08.117
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发表时间：
2010-10-01
影响因子：
3.1
通讯作者：
Nakajima, Kazunori
中科院分区：
文献类型：
--
作者：
Kubo, Ken-ichiro;Tomita, Kenji;Uto, Asuka;Kuroda, Keisuke;Seshadri, Saurav;Cohen, Jared;Kaibuchi, Kozo;Kamiya, Atsushi;Nakajima, Kazunori
精神分裂症1型（DISC 1）是一个有希望的主要精神障碍的遗传危险因素。许多研究小组通过使用RNA干扰（RNAi）方法反复报道了DISC 1在各种品系小鼠和大鼠脑发育中的作用。尽管如此，由于其分子配置的复杂性，如许多剪接变异体和自发缺失的DISC 1基因的编码外显子在一些小鼠品系，有争议的解释这些已发表的数据。因此，在这项研究中，我们解决了这个问题的DISC 1敲低通过短发夹RNA（shRNA）对几个不同的靶序列与一个以上的交付方法到几个小鼠品系，包括C57 BL/6，ICR，和129 X1/SvJ。在这里，我们表明，DISC 1敲低子宫内电穿孔的shRNA对外显子2，6和10一致的结果在发育中的大脑皮层，这是成功地拯救全长DISC 1的共表达神经元迁移缺陷。此外，慢病毒介导的shRNA也导致迁移缺陷，这与已经发表的其他两种方法，如质粒介导和逆转录病毒介导的方法一致。Song的小组先前的研究也报道，在成年海马中，通过靶向外显子2的shRNA敲低DISC 1引起的表型在C57 BL/6和129 S6小鼠中一致可见。综上所述，我们提出，DISC 1基因的外显子2，6和10的shRNA敲低DISC 1亚型的一些是可行的，通常在各种小鼠品系和大鼠神经元迁移发挥关键作用。
Disrupted-in-Schizophrenia 1 (DISC1) is a promising genetic risk factor for major mental disorders. Many groups repeatedly reported a role for DISC1 in brain development in various strains of mice and rats by using RNA interference (RNAi) approach. Nonetheless, due to the complexity of its molecular disposition, such as many splice variants and a spontaneous deletion in a coding exon of the DISC1 gene in some mouse strains, there have been debates on the interpretation on these published data. Thus, in this study, we address this question by DISC1 knockdown via short-hairpin RNAs (shRNAs) against several distinct target sequences with more than one delivery methodologies into several mouse strains, including C57BL/6, ICR, and 129X1/SvJ. Here, we show that DISC1 knockdown by in utero electroporation of shRNA against exons 2, 6, and 10 consistently results in neuronal migration defects in the developing cerebral cortex, which are successfully rescued by co-expression of full-length DISC1. Furthermore, lentivirus-mediated shRNA also led to migration defects, which is consistent with two other methodologies already published, such as plasmid-mediated and retrovirus-mediated ones. The previous study by Song’s group also reported that, in the adult hippocampus, the phenotype elicited by DISC1 knockdown with shRNA targeting exon 2 was consistently seen in both C57BL/6 and 129S6 mice. Taken together, we propose that some of DISC1 isoforms that are feasible to be knocked down by shRNAs to exon 2, 6, and 10 of the DISC1 gene play a key role for neuronal migration commonly in various mouse strains and rats.
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DOI：
10.1073/pnas.0511189103
发表时间：
2006-03-07
影响因子：
11.1
作者：
Koike, H;Arguello, PA;Gogos, JA
通讯作者：
Gogos, JA
影响因子：
21.3
作者：
Kamiya, A;Kubo, K;Sawa, A
通讯作者：
Sawa, A
影响因子：
21.3
作者：
Kawauchi, T;Chihama, K;Hoshino, M
通讯作者：
Hoshino, M
影响因子：
25
作者：
Hayashi-Takagi, Akiko;Takaki, Manabu;Graziane, Nick;Seshadri, Saurav;Murdoch, Hannah;Dunlop, Allan J.;Makino, Yuichi;Seshadri, Anupamaa J.;Ishizuka, Koko;Srivastava, Deepak P.;Xie, Zhong;Baraban, Jay M.;Houslay, Miles D.;Tomoda, Toshifumi;Brandon, Nicholas J.;Kamiya, Atsushi;Yan, Zhen;Penzes, Peter;Sawa, Akira
通讯作者：
Sawa, Akira
影响因子：
56.9
作者：
Brummelkamp, TR;Bernards, R;Agami, R
通讯作者：
Agami, R