Behavioural characterization of Vitamin D receptor knockout mice
Behavioural characterization of Vitamin D receptor knockout mice
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DOI：
10.1016/j.bbr.2004.07.008
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发表时间：
2005-02-28
影响因子：
2.7
通讯作者：
Mackay-Sim, A
中科院分区：
文献类型：
--
作者：
Burne, THJ;McGrath, JJ;Mackay-Sim, A
维生素D（骨化三醇）是一种通过核激素受体（VDR）发挥作用的核转录调节因子。除了在钙和磷酸盐激素平衡的调节和骨形成中的作用外，维生素D还被认为与脑功能有关。本研究的目的是行为表型VDR敲除小鼠。我们通过对VDR无效突变小鼠和野生型同窝对照小鼠进行一系列测试来表征其行为，包括初级行为筛选（使用SHIRPA方案）、旋转棒、步态分析、Y-迷宫、大理石掩埋测试、寝具测试、洞板测试、高架十字迷宫、旷场测试和声惊吓反应的前脉冲抑制。基因型对SHIRPA方案的大多数评分没有影响，除了VDR -/-小鼠有脱发，比VDR +/+小鼠更矮，体重更轻。VDR -/-小鼠具有较短的步态以及在旋转杆上的损伤，在寝具测试中以及在开放领域和声学惊吓反应中的习惯性受损。VDR -/-小鼠具有正常的声惊吓反应，但在长（256 ms）但不短（64 ms）的前脉冲至脉冲间隔时具有受损的PPI。VDR -/-小鼠在开阔场地活动较少，在大理石埋藏测试中埋藏的大理石较少。然而，在高架十字迷宫的开放臂上花费的时间或通过Y迷宫上的重复臂条目评估的工作记忆中没有差异。因此，似乎VDR -/-小鼠具有显著影响运动行为的肌肉和运动障碍，但似乎没有认知障碍，如探索、工作记忆或焦虑所示。(C)2004 Elsevier B. V.保留所有权利。
Vitamin D (calcitriol) is a nuclear transcription regulator acting via a nuclear hormone receptor (VDR). In addition to its role in the regulation of calcium and phosphate horneostasis and in bone formation, Vitamin D is also thought to be involved in brain function. The aim of this study was to behaviourally phenotype VDR knockout mice. We characterized the behaviour of VDR null mutant mice and wildtype littermate controls by subjecting them to a range of tests including a primary behavioural screen (using the SHIRPA protocol), rotarod, gait analysis, Y-maze, marble burying test, bedding test, holeboard test, elevated plus maze, open field test and prepulse inhibition of the acoustic startle response. There were no effects of genotype on most of the scores from the SHIRPA protocol except that VDR -/- mice had alopecia, were shorter and weighed less than VDR +/+ mice. VDR -/- mice had a shorter gait as well as impairments on the rotarod, in the bedding test and impaired habituation in both the open field and on the acoustic startle response. The VDR -/- mice had normal acoustic startle responses but had impaired PPI at long (256 ms) but not short (64 ms) prepulse to pulse intervals. The VDR -/- mice were less active in the open field and buried fewer marbles in the marble burying test. However, there were no differences in the time spent on the open arms of the elevated plus maze or in working memory as assessed by repeat arm entries on the Y-maze. Therefore, it appears that VDR -/- mice have muscular and motor impairments that significantly affects locomotor behaviour but seemingly no impairments in cognition as indicated by exploration, working memory or anxiety. (C) 2004 Elsevier B.V. All rights reserved.