延长julius癫痫,一个爆炸敏感基因,作为研究癫痫发生的模型:冷休克,和一个新的插入突变。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2018-01-02 Epub Date: 2017-12-08 DOI:10.1080/19336934.2017.1402993
Derek Dean, Hannah Weinstein, Seema Amin, Breelyn Karno, Emma McAvoy, Ronald Hoy, Andrew Recknagel, Casey Jarvis, David Deitcher
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引用次数: 4

摘要

果蝇bang-sensitive (BS)突变体是研究癫痫的重要模型。我们最近发现了一个新的BS位点,julius癫痫(jus),编码一个包含两个跨膜结构域和一个细胞外富含半胱氨酸环的蛋白质。我们还通过重组、缺陷定位、互补测试和基因修复确定了先前发现的BS突变jussda iso7.8是jus的等位基因。RNAi敲除表明jus表达在胆碱能神经元中很重要,且jus表达的关键阶段是蛹期中期。最后,我们发现一个功能性的、gfp标记的jus基因组结构主要在颈连接体和胸腹神经节的轴突中表达。在这篇Extra View文章中,我们发现MiMiC gfp标记的Jus定位于与gfp标记的基因组结构相同的神经系统区域,但其表达主要局限于细胞体,并引起bang敏感性。MiMiC gfp标签位于细胞外环,而基因组结构体位于c端。这表明GFP标签的替代位置可能通过改变其亚细胞定位和/或稳定性来破坏Jus蛋白的功能。我们还表明,一小部分表达just的神经元负责BS表型。最后,扩展BS癫痫模型的实用性,我们发现jus突变体表现出冷敏感性麻痹,并且对频闪诱发的癫痫发作部分敏感。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Extending julius seizure, a bang-sensitive gene, as a model for studying epileptogenesis: Cold shock, and a new insertional mutation.

Extending julius seizure, a bang-sensitive gene, as a model for studying epileptogenesis: Cold shock, and a new insertional mutation.

Extending julius seizure, a bang-sensitive gene, as a model for studying epileptogenesis: Cold shock, and a new insertional mutation.

The bang-sensitive (BS) mutants of Drosophila are an important model for studying epilepsy. We recently identified a novel BS locus, julius seizure (jus), encoding a protein containing two transmembrane domains and an extracellular cysteine-rich loop. We also determined that jussda iso7.8, a previously identified BS mutation, is an allele of jus by recombination, deficiency mapping, complementation testing, and genetic rescue. RNAi knockdown revealed that jus expression is important in cholinergic neurons and that the critical stage of jus expression is the mid-pupa. Finally, we found that a functional, GFP-tagged genomic construct of jus is expressed mostly in axons of the neck connectives and of the thoracic abdominal ganglia. In this Extra View article, we show that a MiMiC GFP-tagged Jus is localized to the same nervous system regions as the GFP-tagged genomic construct, but its expression is mostly confined to cell bodies and it causes bang-sensitivity. The MiMiC GFP-tag lies in the extracellular loop while the genomic construct is tagged at the C-terminus. This suggests that the alternate position of the GFP tag may disrupt Jus protein function by altering its subcellular localization and/or stability. We also show that a small subset of jus-expressing neurons are responsible for the BS phenotype. Finally, extending the utility of the BS seizure model, we show that jus mutants exhibit cold-sensitive paralysis and are partially sensitive to strobe-induced seizures.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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