Fmr1 knockout mice are impaired in a leverpress escape/avoidance task
Fmr1 knockout mice are impaired in a leverpress escape/avoidance task
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DOI：
10.1111/j.1601-183x.2005.00183.x
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发表时间：
2006-08-01
影响因子：
2.5
通讯作者：
Paylor, R.
中科院分区：
文献类型：
--
作者：
Brennan, F. X.;Albeck, D. S.;Paylor, R.
脆性X综合征（FXS）是遗传性智力低下（MR）的最常见形式。FXS通常由Fmr 1基因的突变引起（Verkerk等，1991，Cell 65，905-914）。为了更好地理解Fmr 1及其基因产物脆性X智力迟钝蛋白（FMRP）在中枢神经系统功能中的作用，研究人员已经转向使用动物模型系统来产生FMRP缺陷的Fmr 1敲除（KO）小鼠（Bakker等，1994，Cell 78，23-33）。不幸的是，许多研究发现在Fmr 1 KO小鼠中没有一致的，稳健的学习和记忆障碍。我们进行了一项研究，以评估Fmr 1 KO和野生型（WT）动物在应激逃避/回避范式中的表现。在4个每日1小时的阶段中研究了Fmr 1 KO和WT同窝仔。与WT小鼠相比，Fmr 1 KO小鼠的回避和总反应较少。KO动物不仅缺乏回避，而且因子内方差分析显示，它们没有获得任何明显程度的应激反应。研究期间的观察结果表明，Fmr 1 KO动物对电击有明显反应，消除了对缺陷的明显感官解释。其他研究发现，与WT对照组相比，KO小鼠显示出增加的探索和运动活动，这一事实反对运动缺陷。未来的研究将试图描述行为缺陷的性质，并试图用多巴胺能或多巴胺能药物挽救这种反应。
Fragile X syndrome (FXS) is the most common form of inherited mental retardation (MR). FXS is typically caused by a mutation of the Fmr1 gene (Verkerk et al. 1991, Cell 65, 905-914). To better understand the role of Fmr1 and its gene product fragile X mental-retardation protein (FMRP) in central nervous system function, researchers have turned to the use of animal model systems to generate an Fmr1 knockout (KO) mouse that is deficient in FMRP (Bakker et al. 1994, Cell 78, 23-33). Unfortunately, a number of studies have found no consistent, robust learning and memory impairment in the Fmr1 KO mice. We conducted a study to assess the performance of Fmr1 KO and wildtype (WT) animals in a leverpress escape/avoidance paradigm. Fmr1 KO and WT littermates were studied in four daily 1-h sessions. The Fmr1 KO mice performed fewer avoidance and total responses than WT mice. The KO animals were not simply deficient in avoidance, but a within-factor ANOVA revealed that they did not acquire the leverpress response to any appreciable degree. Observation during the sessions indicated that the Fmr1 KO animals clearly responded to the shock, eliminating an obvious sensory explanation for the deficit. The fact that other studies have found that the KO mice displayed increased exploratory and locomotor activity compared with WT controls argues against a motoric deficit. Future studies will attempt to delineate the nature of the behavioral deficit as well as attempt to rescue the response with glutamatergic or dopaminergic agents.