Phenotypic analysis of catastrophic childhood epilepsy genes.
Phenotypic analysis of catastrophic childhood epilepsy genes.
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DOI：
10.1038/s42003-021-02221-y
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发表时间：
2021-06-03
影响因子：
5.9
通讯作者：
Baraban SC
中科院分区：
文献类型：
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作者：
Griffin A;Carpenter C;Liu J;Paterno R;Grone B;Hamling K;Moog M;Dinday MT;Figueroa F;Anvar M;Ononuju C;Qu T;Baraban SC
基因工程技术促进了斑马鱼在基因功能研究中的广泛应用，但是基于斑马鱼的人类疾病研究，特别是神经系统疾病的研究是有限的。在这里，我们使用CRISPR-Cas9生成了40条代表灾难性儿童癫痫的单基因突变斑马鱼系。我们使用电生理、行为、神经解剖、生存和药理学分析来评估幼虫的表型。使用局部田间电位记录（LFP）筛选约3300只幼虫。在斑马鱼品系中鉴定了8个基因具有无端电图癫痫活动（即癫痫）的表型；ARX、EEF1A、GABRB3、GRIN1、PNPO、SCN1A、STRADA和STXBP1。我们还创建了一个包含测序信息、生存曲线、行为特征和代表性电生理数据的开源数据库。我们将所有斑马鱼系作为神经科学界的资源，并将其作为进一步功能分析和/或新疗法鉴定的起点。Griffin等人使用CRISPR-Cas9生成了40个代表儿童癫痫的单基因突变斑马鱼系，他们使用电生理、行为、神经解剖、生存和药理学分析来评估幼虫的表型。他们的研究为未来的功能分析和/或确定潜在的抗癫痫疗法提供了有用的资源。
Genetic engineering techniques have contributed to the now widespread use of zebrafish to investigate gene function, but zebrafish-based human disease studies, and particularly for neurological disorders, are limited. Here we used CRISPR-Cas9 to generate 40 single-gene mutant zebrafish lines representing catastrophic childhood epilepsies. We evaluated larval phenotypes using electrophysiological, behavioral, neuro-anatomical, survival and pharmacological assays. Local field potential recordings (LFP) were used to screen ∼3300 larvae. Phenotypes with unprovoked electrographic seizure activity (i.e., epilepsy) were identified in zebrafish lines for 8 genes; ARX, EEF1A, GABRB3, GRIN1, PNPO, SCN1A, STRADA and STXBP1. We also created an open-source database containing sequencing information, survival curves, behavioral profiles and representative electrophysiology data. We offer all zebrafish lines as a resource to the neuroscience community and envision them as a starting point for further functional analysis and/or identification of new therapies. Griffin et al used CRISPR-Cas9 to generate 40 single-gene mutant zebrafish lines representing childhood epilepsies for which they evaluated larval phenotypes using electrophysiological, behavioral, neuro-anatomical, survival and pharmacological assays. Their study provides a useful resource for the future functional analysis and/or identification of potential anti-epileptic therapies.
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影响因子：
5.6
作者：
Cornet C;Di Donato V;Terriente J
通讯作者：
Terriente J
影响因子：
3.7
作者：
Grone BP;Marchese M;Hamling KR;Kumar MG;Krasniak CS;Sicca F;Santorelli FM;Patel M;Baraban SC
通讯作者：
Baraban SC
影响因子：
14.5
作者：
Griffin, Aliesha;Hamling, Kyla R.;Baraban, Scott C.
通讯作者：
Baraban, Scott C.
影响因子：
5.6
作者：
Berg, Anne T.;Berkovic, Samuel F.;Scheffer, Ingrid E.
通讯作者：
Scheffer, Ingrid E.
影响因子：
64.8
作者：
通讯作者：
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