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雌性锌转运体3(ZnT3)基因敲除小鼠的行为特征

Behavioral characterization of female zinc transporter 3 (ZnT3) knockout mice.

作者信息

Thackray Sarah E, McAllister Brendan B, Dyck Richard H

机构信息

Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.

Department of Psychology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada.

出版信息

Behav Brain Res. 2017 Mar 15;321:36-49. doi: 10.1016/j.bbr.2016.12.028. Epub 2016 Dec 21.

DOI:10.1016/j.bbr.2016.12.028
PMID:28012850
Abstract

Zinc is an important element in all cells of the body, having structural, enzymatic, and regulatory functions. In some neurons, zinc is loaded into synaptic vesicles by zinc transporter 3 (ZnT3) and released into the synaptic cleft, where it can modulate neuronal function. ZnT3 knockout (KO) mice lack ZnT3 and thus lack synaptic zinc. Previous studies have examined the behavioral phenotype of ZnT3 KO mice, mostly using mixed-sex or male-only groups. In the present study we focused specifically on the behavior of female ZnT3 KO mice (2-3 months old). An extensive battery of tests was administered to assess sensorimotor and cognitive behaviours, as well as to examine for a possible schizophrenia-like phenotype. ZnT3 KO mice performed similarly to wild type controls in the majority of tests. However, they were less accurate in the skilled reach task, suggesting impaired skilled motor learning, and faster to descend a vertical pole. ZnT3 KO mice were also slower in the open field and made fewer chamber entries in the social preference test, suggesting decreased exploratory locomotion. No differences were observed in the Morris water task or fear conditioning test. This is the first study to show a behavioural phenotype specifically for female ZnT3 KO mice. Comparing our results to previous studies, it appears that there may be sex-specific effects of eliminating ZnT3. Female ZnT3 KO mice exhibit abnormalities in locomotion and at skilled motor learning, but we were unable to detect spatial or fear learning deficits previously described in male ZnT3 KO mice.

摘要

锌是人体所有细胞中的一种重要元素,具有结构、酶促和调节功能。在一些神经元中,锌通过锌转运体3(ZnT3)被装载到突触小泡中,并释放到突触间隙,在那里它可以调节神经元功能。ZnT3基因敲除(KO)小鼠缺乏ZnT3,因此缺乏突触锌。先前的研究已经考察了ZnT3 KO小鼠的行为表型,大多使用混合性别或仅雄性的群体。在本研究中,我们特别关注2至3月龄雌性ZnT3 KO小鼠的行为。进行了一系列广泛的测试以评估感觉运动和认知行为,以及检查是否存在可能的精神分裂症样表型。在大多数测试中,ZnT3 KO小鼠的表现与野生型对照组相似。然而,它们在熟练够物任务中的准确性较低,表明熟练运动学习受损,并且在垂直杆上下降得更快。ZnT3 KO小鼠在旷场实验中也较慢,并且在社会偏好测试中进入隔室的次数较少,表明探索性运动减少。在莫里斯水迷宫任务或恐惧条件测试中未观察到差异。这是第一项专门展示雌性ZnT3 KO小鼠行为表型的研究。将我们的结果与先前的研究进行比较,似乎消除ZnT3可能存在性别特异性效应。雌性ZnT3 KO小鼠在运动和熟练运动学习方面表现异常,但我们未能检测到先前在雄性ZnT3 KO小鼠中描述的空间或恐惧学习缺陷。

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