Assessment of learning by the Morris water task and fear conditioning in inbred mouse strains and F-1 hybrids: Implications of genetic background for single gene mutations and quantitative trait loci analyses

Assessment of learning by the Morris water task and fear conditioning in inbred mouse strains and F-1 hybrids: Implications of genetic background for single gene mutations and quantitative trait loci analyses
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DOI:
10.1016/s0306-4522(97)00165-6
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发表时间:
1997-10-01
期刊:
影响因子:
3.3
通讯作者:
Wehner, JM
Wehner, JM
中科院分区:
医学3区
文献类型:
--
作者:
Owen, EH;Logue, SF;Wehner, JM

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遗传学方法,包括创建转基因或零突变模型,以及使用数量性状基因座策略进行定位研究,可以用来在小鼠中识别调节学习过程的候选基因。关于单基因突变对学习等多基因行为的影响的解释,部分取决于用于这些操作的动物的遗传背景。为了解决遗传变异的问题,对12个近交系和7个不同的F-1杂交种进行了多项行为任务的测试,其中包括两种复杂的学习范式:莫里斯水任务和恐惧条件作用。所有测量变量的应变差异均被发现。在莫里斯任务的隐藏平台版本中,白化动物表现不佳,而总体而言,F-1杂交显示出对训练象限的最佳选择性,这在探测器试验中进行了测量。相比之下,几乎所有的基因类型在情景恐惧条件反射任务中都表现良好,并学会了将测试环境与脚电击和听觉刺激的配对联系起来,就像训练24小时后,与改变的环境相比,测试环境中的冰冻程度增加所表明的那样。行为指标的显著遗传相关性表明,相同的基因控制着行为任务的各个方面的表现。这些近亲繁殖的品系和F-1杂交品系的分数提供了恐惧条件反射和Morris水任务的学习能力的基线水平。本研究的结果证实了遗传背景在执行各种学习任务中的重要性。在开发新的转基因或零突变动物模型时,应考虑这种可变性。(C)1997年IBRO。爱思唯尔科学有限公司出版。
Genetic methods including the creation of transgenic or null mutant models and mapping studies using quantitative trait loci strategies can be used to identify candidate genes in mice that regulate learning processes. Interpretations as to the impact of single gene mutations for polygenic behaviours like learning will depend in part on the genetic background of the animals used for these manipulations. To address the issue of genetic variability, 12 inbred strains and seven different F-1 hybrids were tested on multiple behavioural tasks, including two complex learning paradigms: the Morris water task and fear conditioning. Strain differences were found for all variables measured. In the hidden platform version of the Morris task, the albino animals performed poorly while overall the F-1 hybrids showed the best selectivity for the trained quadrant as measured in a probe trial. In contrast, almost all genotypes performed well on the contextual fear conditioning task and learned to associate the test context with the pairing of a foot shock and auditory stimulus as demonstrated 24 h after training by increased freezing in the test environment compared to an altered context. Significant genetic correlations were obtained for behavioural measures suggesting that the same genes regulate various aspects of performance on behavioural tasks.Scores from these multiple inbred strains and F-1 hybrids provide a baseline level of learning ability for fear conditioning and the Morris water task. The results of the present study confirm the importance of genetic background in the performance of various learning tasks. This variability should be considered when developing new transgenic or null mutant animal models. (C) 1997 IBRO. Published by Elsevier Science Ltd.