Behavioral analysis of CREB αΔ mutation on a B6/129 F1 hybrid background
Behavioral analysis of CREB αΔ mutation on a B6/129 F1 hybrid background
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DOI：
10.1002/hipo.10003
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发表时间：
2002-01-01
期刊：
影响因子：
3.5
通讯作者：
Abel, T
中科院分区：
文献类型：
--
作者：
Graves, L;Dalvi, A;Abel, T
环腺苷酸（cAMP）反应元件结合蛋白（CREB）是一种活性依赖性转录因子，在失智症、果蝇和啮齿类动物的突触可塑性和记忆储存中发挥作用。两种CREB同种型（α和δ; CREB α δ小鼠）靶向缺失的小鼠已在C57 BL/6（B6）和129/SvEv（129）的混合遗传背景以及B6和FVB/N的确定F1杂交体上进行了表征，这些结果表明CREB A小鼠的表型严重依赖于遗传背景。在检查CREB在学习和记忆中的作用可能受品系差异影响的假设中，我们分析了B6和129品系F1杂交背景下CREB α Delta突变的小鼠。在这种背景下，CREB alpha Delta小鼠在Morris水迷宫中的短期和长期线索和背景恐惧条件反射以及正常的空间学习受损。我们的研究结果表明，CREB α Delta小鼠海马功能的至少某些方面是正常的，并且CREB α Delta小鼠在136/129 F1背景下杏仁核功能发生了改变。这些研究强调了在基因敲除和转基因小鼠的行为分析中控制遗传背景的重要性。(C)2002 Wiley-Liss，Inc.
The cyclic AMP (cAMP)-response element binding protein (CREB) is an activity-dependent transcription factor that plays a role in synaptic plasticity and memory storage in Aplysia, Drosophila, and rodents. Mice with targeted deletions of two CREB isoforms (alpha and Delta; CREB alphaDelta mice) have been characterized on a mixed genetic background of C57BL/6 (B6) and 129/SvEv (129), as well as on a defined F1 hybrid of B6 and FVB/N, and these results suggest that the phenotype of CREB A mice depends critically on genetic background. In an examination of the hypothesis that the role of CREB in learning and memory can be influenced by strain differences, we analyzed mice with the CREB alphaDelta mutation on an F1 hybrid background of B6 and 129 strains. CREB alphaDelta mice on this background had impaired short-term and long-term cued and contextual fear conditioning and normal spatial learning in the Morris water maze. Our results suggest that at least some aspects of hippocampal function are normal in CREB alphaDelta mice, and that CREB alphaDelta mice on the 136/129 F1 background have alterations in amygdala function. These studies underscore the importance of controlling for genetic background in the behavioral analysis of knockout and transgenic mice. (C) 2002 Wiley-Liss, Inc.