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敲除Zbtb33基因会导致小鼠的运动能力、探索行为和前脉冲抑制增强。

Knockout Zbtb33 gene results in an increased locomotion, exploration and pre-pulse inhibition in mice.

作者信息

Kulikov Alexander V, Korostina Valeria S, Kulikova Elizabeth A, Fursenko Dariya V, Akulov Andrey E, Moshkin Mikhail P, Prokhortchouk Egor B

机构信息

Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk 630090, Russia.

Centre "Bioengineering", Russian Academy of Sciences, Moscow 117312, Russia.

出版信息

Behav Brain Res. 2016 Jan 15;297:76-83. doi: 10.1016/j.bbr.2015.10.003. Epub 2015 Oct 22.

Abstract

The Zbtb33 gene encodes the Kaiso protein-a bimodal transcriptional repressor. Here, the effects of Zbtb33 gene disruption on the brain and behaviour of the Kaiso-deficient (KO) and C57BL/6 (WT) male mice were investigated. Behaviour was studied using the open field, novel object, elevated plus maze and acoustic startle reflex tests. Brain morphology was investigated with magnetic resonance imaging. Biogenic amine levels and gene expression in the brain were measured with high-performance liquid chromatography and quantitative real-time RT-PCR, respectively. Zbtb33 gene mRNA was not detected in the brain of KO mice. KO mice exhibited increased locomotion, exploration in the open field, novel object and elevated plus-maze test. At the same time, Zbtb33 gene disruption did not alter anxiety-related behaviour in the elevated plus-maze test. KO mice showed elevated amplitudes and pre-pulse inhibitions of the acoustic startle reflex. These behavioural alterations were accompanied by significant reductions in the volumes of the lateral ventricles without significant alterations in the volumes of the hippocampus, striatum, thalamus and corpus callosum. Norepinephrine concentration was reduced in the hypothalami and hippocampi in KO mice, while the levels of serotonin, dopamine, their metabolites as well as mRNA of the gene coding brain-derived neurotrophic factor were not altered in the brain of KO mice compared to WT mice. This study is the first to reveal the involvement of the Zbtb33 gene in the regulation of behaviour and the central nervous system.

摘要

Zbtb33基因编码Kaiso蛋白——一种双峰转录抑制因子。在此,研究了Zbtb33基因破坏对Kaiso缺陷(KO)和C57BL/6(WT)雄性小鼠大脑和行为的影响。使用旷场试验、新物体试验、高架十字迷宫试验和听觉惊吓反射试验研究行为。用磁共振成像研究脑形态。分别用高效液相色谱法和定量实时逆转录聚合酶链反应测量脑中生物胺水平和基因表达。在KO小鼠的脑中未检测到Zbtb33基因mRNA。KO小鼠在旷场试验、新物体试验和高架十字迷宫试验中表现出运动增加和探索行为。同时,Zbtb33基因破坏在高架十字迷宫试验中未改变焦虑相关行为。KO小鼠表现出听觉惊吓反射的振幅增加和前脉冲抑制。这些行为改变伴随着侧脑室体积的显著减小,而海马体、纹状体、丘脑和胼胝体的体积没有显著改变。KO小鼠下丘脑和海马体中的去甲肾上腺素浓度降低,而与WT小鼠相比,KO小鼠脑中血清素、多巴胺、它们的代谢产物以及编码脑源性神经营养因子的基因的mRNA水平没有改变。本研究首次揭示了Zbtb33基因参与行为和中枢神经系统的调节。

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