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在 C57BL/6 背景下培育的 p300/CBP 相关因子(PCAF)组蛋白乙酰转移酶基因敲除小鼠中,工作记忆改变,但焦虑或应激反应无改变。

Alteration of working memory but not in anxiety or stress response in p300/CBP associated factor (PCAF) histone acetylase knockout mice bred on a C57BL/6 background.

机构信息

INSERM U 710, 34095 Montpellier, France.

出版信息

Neurosci Lett. 2010 May 21;475(3):179-83. doi: 10.1016/j.neulet.2010.03.077. Epub 2010 Apr 4.

Abstract

P300/CBP associated factor (PCAF) acts as an acetyltransferase that acetylates specific lysine residues in histones, thereby remodelling chromatin structure. The possible involvement of PCAF in learning and memory processes or mood disorders was recently assessed by characterizing the behavioural phenotype of PCAF KO mice bred on a CD1 background and revealed short-term memory deficits that evolved with age towards long-term memory alteration and an exaggerated response to stress [10]. PCAF KO mice have been backcrossed on a C57BL/6j strain for 15 generations and we report here the first data regarding their behavioural phenotype. PCAF KO mice bred on a C57 background showed short-term memory deficits in terms of decreased spontaneous alternation and absence of acquisition of a daily changing platform position in the water-maze. Acquisition of a fixed platform location or passive avoidance response was preserved. PCAF KO mice showed no difference with WT C57BL/6j controls in their performances in the forced swimming and light/dark exploration box, suggesting no particular phenotype on anxiety and stress responses. We therefore evidenced marked phenotypic differences in PCAF KO mice depending on the genetic background strain confirming that PCAF histone acetyltransferase is involved lifelong in the chromatin remodelling necessary for memory formation but differentially involved in anxiety and response to stress.

摘要

P300/CBP 相关因子(PCAF)作为乙酰转移酶,可使组蛋白特定赖氨酸残基乙酰化,从而重塑染色质结构。最近通过对 CD1 背景下培育的 PCAF KO 小鼠的行为表型进行特征分析,评估了 PCAF 可能参与学习和记忆过程或情绪障碍,结果显示,这些小鼠存在短期记忆缺陷,随着年龄的增长逐渐发展为长期记忆改变和对压力的过度反应[10]。PCAF KO 小鼠已在 C57BL/6j 品系上进行了 15 代回交,我们在此报告了它们行为表型的首批数据。在 C57 背景下培育的 PCAF KO 小鼠在自发交替减少和水迷宫中每日变化平台位置的获得能力缺失方面表现出短期记忆缺陷。固定平台位置或被动回避反应的获得能力得以保留。PCAF KO 小鼠在强迫游泳和明暗探索箱中的表现与 WT C57BL/6j 对照无差异,这表明它们在焦虑和应激反应方面没有特定表型。因此,我们根据遗传背景品系证实了 PCAF KO 小鼠存在明显的表型差异,这表明 PCAF 组蛋白乙酰转移酶终生参与记忆形成所需的染色质重塑,但在焦虑和应激反应方面的参与程度不同。

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