CRISPR/Cas9-induced nos2b mutant zebrafish display behavioral abnormalities,Genes, Brain and Behavior

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CRISPR/Cas9-induced nos2b mutant zebrafish display behavioral abnormalities
Genes, Brain and Behavior ( IF 2.4 ) Pub Date : 2020-11-16 , DOI: 10.1111/gbb.12716
Lei Gao ₁ , Rachit Penglee ₁ , Yajuan Huang ₁ , Xinxin Yi ₁ , Xiaojie Wang ₁ , Liping Liu ₁ , Xiaoling Gong ₁ , Baolong Bao ₁

Affiliation

The immunomodulatory function of nitric oxide synthase (NOS2) has been extensively studied. However, some behavioral abnormalities caused by its mutations have been found in a few rodent studies, of which the molecular mechanism remains elusive. In this research, we generated nos2b gene knockout zebrafish (nos2b^sou2/sou2) using CRISPR/Cas9 approach and investigated their behavioral and molecular changes by doing a series of behavioral detections, morphological measurements, and molecular analyses. We found that, compared with nos2b^+/+ zebrafish, nos2b^sou2/sou2 zebrafish exhibited enhanced motor activity; additionally, nos2b^sou2/sou2 zebrafish were characterized by smaller brain size, abnormal structure of optic tectum, reduced mRNA level of presynaptic synaptophysin and postsynaptic homer1, and altered response to sodium nitroprusside/methylphenidate hydrochloride treatment. These findings will likely contribute to future studies of behavioral regulation.

中文翻译：

CRISPR/Cas9 诱导的 nos2b 突变斑马鱼表现出行为异常

一氧化氮合酶（NOS2）的免疫调节功能已被广泛研究。然而，在一些啮齿动物研究中发现了一些由其突变引起的行为异常，其中分子机制仍然难以捉摸。在这项研究中，我们使用 CRISPR/Cas9 方法生成了 nos2b基因敲除斑马鱼 ( nos2b ^sou2/sou2 )，并通过进行一系列行为检测、形态测量和分子分析来研究它们的行为和分子变化。我们发现，与nos2b ^+/+斑马鱼相比，nos2b ^sou2/sou2斑马鱼表现出增强的运动活动；此外，nos2b ^sou2/sou2斑马鱼的特点是大脑较小，视顶盖结构异常，突触前突触素和突触后homer1的mRNA水平降低，对硝普钠/哌醋甲酯治疗的反应改变。这些发现可能有助于未来的行为调节研究。

更新日期：2020-11-16

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