Phenotypic segregation of aphakia and Pitx3-null mutants reveals that Pitx3 deficiency increases consolidation of specific movement components
Phenotypic segregation of aphakia and Pitx3-null mutants reveals that Pitx3 deficiency increases consolidation of specific movement components
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DOI：
10.1016/j.bbr.2007.08.032
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发表时间：
2008-01-25
影响因子：
2.7
通讯作者：
Smidt, Marten P.
中科院分区：
文献类型：
--
作者：
Kas, Martien J. H.;Van der Linden, Annemarie J. A.;Smidt, Marten P.
无晶状体（ak）小鼠中脑间脑多巴胺（mdDA）神经元特异性转录因子Pitx 3的缺乏导致黑质神经元（SNc）的缺失。同时，自发运动行为减少，症状令人联想到帕金森病。然而，ak小鼠系起源于20世纪60年代，并已与C57 BL/6 J近交系对照进行了比较。因此，为了确定Pitx 3基因在基线和新奇诱导的运动行为和mdDA神经元活性中的功能，我们在受控的遗传和表观遗传背景中分析了Pitx 3缺陷。分析表明，与有争议的和先前报道的ak小鼠的活动减退相反，Pitx 3-/-小鼠显示出正常的暗相运动活动水平。我们的数据还显示，ak和Pitx 3-/-小鼠都显示出相似的神经解剖学和生理表型，有趣的是，在其习惯性睡眠阶段显示出自发的笼内活动水平增加。进一步的行为分析显示，ak和Pitx 3-/-小鼠都减少了转换，但增加了特定运动行为的巩固，如直立和水平运动。因此，Pitx 3不参与夜间运动活动水平的表达，但对选择性mdDA神经元活动至关重要，并与运动的巩固增加相关。(C)2007 Elsevier B. V.保留所有权利。
Deficiency of the meso-diencephalic dopamine (mdDA) neuron specific transcription factor Pitx3 in aphakia (ak) mice results in the loss of the substantia nigra compacta (SNc). Concomitantly, reduced spontaneous locomotor behavior, symptoms reminiscent to those in Parkinson's disease, has been reported. However, the ak mouse line originates from the 1960s and has been compared to C57BL/6J inbred controls. Therefore, to define Pitx3 gene function in baseline and novelty-induced locomotor behavior and mdDA neuronal activity, we analyzed Pitx3-deficiency in a controlled genetic and epigenetic background. The analysis implicated that, in contrast to the controversial and previously reported hypo-activity in ak mice, Pitx3-/- mice showed normal dark phase motor activity levels. Our data also revealed that ak and Pitx3-/- mice both display a similar neuro-anatomical and physiological phenotype, and, interestingly, showed increased spontaneous home cage activity levels during their habitual sleep phase. Further behavioral analysis revealed that both ak and Pitx3-/- mice have reduced transitions but increased consolidation of specific locomotor behaviors, such as rearing and horizontal movement. Thus, Pitx3 is not involved in the expression of nighttime motor activity levels, but is critical for selective mdDA neuronal activity and associated with increased consolidation of movement. (C) 2007 Elsevier B.V. All rights reserved.